KIDO Shinsuke

Researcher Information

Degree

• (BLANK)

URL

http://kindaiagri-clinutr.wixsite.com/rinsyoueiyouken

Research funding number

• 30437652

J-Global ID

• 200901088459764510

Research Interests

• 血管石灰化   骨粗鬆症   腎不全   老化   骨不全   リン   ビタミンD   g   Wnt   グルココルチコイド   ΔFosB   FGF23   骨髄腫   リン代謝   血管内皮機能   NAD   血管新生   慢性腎臓病   IL-11   遺伝子発現調節   骨形成   骨芽細胞   力学的負荷   Boneformation   Ostreobsts   Mechanical Stress   

Research Areas

• Life sciences / Nephrology
• Life sciences / Metabolism and endocrinology
• Life sciences / Pathobiochemistry
• Life sciences / Cell biology

Academic & Professional Experience

• 2018/04 - Today  KINDAI Research Institute for Agricultural Technology and Innovation研究員
• 2017/04 - Today  Kindai UniversityMajor in Advanced life Science, Graduate School of Agriculture准教授
• 2013/04 - Today  Kindai UniversityFaculty of Agriculture, Department of Food Science and Nutrition准教授
• 2010/11 - 2013/03  The University of TokushimaInstitute of Health Biosciences The University of Tokushima Graduate School特任助教
• 2011 - 2012  The University of Tokushima大学院・ヘルスバイオサイエンス研究部
• 2008/04 - 2010/10  The University of TokushimaInstitute of Health Biosciences The University of Tokushima Graduate School学術研究員
• 2003/10 - 2008/03  The University of TokushimaInstitute of Health Biosciences The University of Tokushima Graduate School21世紀COE特別研究員
• 2002/04 - 2003/09  The University of TokushimaFaculty of Medicine研究員
• 2000/04 - 2002/03  The University of TokushimaFaculty of Medicine日本学術振興会特別研究員 (DC2)

Education

• 1999/04 - 2003/03  The University of Tokushima  栄養学研究科  博士課程後期
• 1997/04 - 1999  The University of Tokushima  栄養学研究科  博士課程前期
•        - 1999  The University of Tokushima  Graduate School, Division of Nutrition
• 1993/04 - 1997/03  The University of Tokushima  Faculty of Medicine  栄養
•        - 1997  The University of Tokushima  Faculty of Medicine

Association Memberships

• 日本摂食嚥下リハビリテーション学会   THE VITAMIN SOCIETY OF JAPAN   THE JAPANESE SOCIETY OF NUTRITION AND DIETETICS   JAPAN SOCIETY OF METABOLISM AND CLINICAL NUTRITION   日本分子生物学会   米国骨代謝学会   日本骨代謝学会   

Published Papers

• Effect of a plant protein‐rich diet on postprandial phosphate metabolism in healthy adult men: a randomised controlled trial

  Kozue Uenishi; Nozomi Kawasaki; Haruka Iseki; Misato Nogata; Yuki Kawabata; Shinsuke Kido

  Journal of Human Nutrition and Dietetics Wiley 0952-3871 2024/03 [Refereed]
   

  Abstract Background This study examined the effects of animal protein‐ and plant protein‐rich diets on postprandial phosphorus metabolism in healthy male subjects. Methods The study was conducted by randomised parallel‐group comparison of healthy men aged 21–24 years. In Study 1, participants were divided into two groups and consumed either a 70% animal protein diet (AD, n = 6) or a 70% plant protein diet (PD, n = 6). In Study 2, participants were divided into three groups and consumed either AD (n = 10), PD (n = 10) or AD + DF, a 70% animal protein diet loaded with the same amount of fibre as PD (n = 9). The phosphorus contents of the diets used in this study were nearly equivalent (AD, 710.1 mg; PD, 709.7 mg; AD + DF, 708.9 mg). Blood and urine samples were collected before, and 2 and 4 h after the meal to measure phosphorus and calcium levels. Results In Study 1, PD consumption resulted in lower blood and urinary phosphorus concentrations 2 h postprandially compared with AD (p < 0.05). In Study 2, blood phosphorus levels in AD + DF after the diet remained lower, but not significantly so compared with AD, and urinary phosphorus levels were significantly lower 2 h postprandially (p < 0.05). Conclusions A plant protein‐rich diet reduced rapid postprandial increases in blood and urinary phosphorus concentrations compared with the animal protein‐rich diets, suggesting that dietary fibre may play a partial role in the postprandial decreases in blood and urinary phosphorus concentrations.
• Effect of various thermal processing methods and pretreatment methods to reduce phosphorus content of chicken meat for CKD patients

  Kozue Uenishi; Keiko Tomita; Shinsuke Kido

  Nutrition and Food Science Emerald 53 (1) 61 - 70 0034-6659 2022/04 [Refereed]
   

  Purpose The management of dietary phosphorus in chronic kidney disease patients is an important issue. Phosphorus is often found with protein in foods. However, excessive protein restriction worsens the nutritional status of the patient; thus, phosphorus must be selectively restricted. This study aims to assess the effects of various pretreatments readily available in ordinary households on phosphorus loss in foodstuffs. Design/methodology/approach This study evaluated the retention of phosphorus in cooked chicken meat (boiled, baked, steamed and microwaved). In addition, this study incorporated various pretreatments (pounding, stabbing, cutting and enzymatic treatment) to the method exhibiting the lowest phosphorus retention (boiling) and assessed the effects on phosphorus retention. Findings Boiling (65%, vs baking, p < 0.001; vs steaming, p = 0.013; vs microwaving, p = 0.002) of the chicken meat resulted in the lowest phosphorus retention compared to the other cooking methods (baking [89%], steaming [73%] and microwaving [75%]). In addition, stabbing (58%, p = 0.009) or cutting (46%, p < 0.001) further reduced the retention of phosphorus in boiled chicken meat. The retention of phosphorus in enzyme-pretreated boiled chicken was reduced by approximately 10% compared to untreated chicken (p = 0.01). The cooking method that reduced phosphorus retention to the greatest extent was enzyme treatment prior to cutting and boiling. Originality/value This paper investigates the effects of common household cooking methods and combinations of methods on the phosphorus content of meat.
• Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse.

  Kaneko I; Segawa H; Ikuta K; Hanazaki A; Fujii T; Tatsumi S; Kido S; Hasegawa T; Amizuka N; Saito H; Miyamoto KI

  Endocrinology 159 (7) 2741 - 2758 0013-7227 2018/07 [Refereed]
   

  X-linked hypophosphatemia (XLH), the most common form of inheritable rickets, is caused by inactivation of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and leads to fibroblast growth factor (FGF) 23-dependent renal inorganic phosphate (Pi) wasting. In the present study, we investigated whether maintaining Pi homeostasis with a potent vitamin D3 analog, eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy) vitamin D3; ED71], could improve hypophosphatemic rickets in a murine model of XLH, the Hyp mouse. Vehicle, ED71, or 1,25-dihydroxyvitamin D was subcutaneously injected five times weekly in wild-type (WT) and Hyp mice for 4 weeks, from 4 to 8 weeks of age. Injection of ED71 into WT mice suppressed the synthesis of renal 1,25-dihydroxyvitamin D and promoted phosphaturic activity. In contrast, administration of ED71 to Hyp mice completely restored renal Pi transport and NaPi-2a protein levels, although the plasma-intact FGF23 levels were further increased. In addition, ED71 markedly increased the levels of the scaffold proteins, renal sodium-hydrogen exchanger regulatory factor 1, and ezrin in the Hyp mouse kidney. Treatment with ED71 increased the body weight and improved hypophosphatemia, the bone volume/total volume, bone mineral content, and growth plate structure in Hyp mice. Thus, ED71 causes FGF23 resistance for phosphate reabsorption and improves rachitic bone phenotypes in Hyp mice. In conclusion, ED71 has opposite effects on phosphate homeostasis in WT and Hyp mice. Analysis of Hyp mice treated with ED71 could result in an additional model for elucidating PHEX abnormalities.
• Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells

  Yuji Shiozaki; Hiroko Segawa; Saori Ohnishi; Akiko Ohi; Mikiko Ito; Ichiro Kaneko; Shinsuke Kido; Sawako Tatsumi; Ken-ichi Miyamoto

  Journal of Medical Investigation University of Tokushima 62 (3) 209 - 218 1349-6867 2015/09 [Refereed]
   

  NaPi-IIc/SLC34A3 is a sodium-dependent inorganic phosphate (Pi) transporter in the renal proximal tubules and its mutations cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In the present study, we created a specific antibody for opossum SLC34A3, NaPi-IIc (oNaPi-IIc), and analyzed its localization and regulation in opossum kidney cells (a tissue culture model of proximal tubular cells). Immunoreactive oNaPi-IIc protein levels increased during the proliferative phase and decreased during differentiation. Moreover, stimulating cell growth upregulated oNaPi-IIc protein levels, whereas suppressing cell proliferation downregulated oNaPi-IIc protein levels. Immunocytochemistry revealed that endogenous and exogenous oNaPi-IIc proteins localized at the protrusion of the plasma membrane, which is a phosphatidylinositol 4,5-bisphosphate (PIP2) rich-membrane, and at the intracellular vacuolar membrane. Exogenous NaPi-IIc also induced cellular vacuoles and localized in the plasma membrane. The ability to form vacuoles is specific to electroneutral NaPi-IIc, and not electrogenic NaPi-IIa or NaPi-IIb. In addition, mutations of NaPi-IIc (S138F and R468W) in HHRH did not cause cellular PIP2-rich vacuoles. In conclusion, our data anticipate that NaPi-IIc may regulate PIP2 production at the plasma membrane and cellular vesicle formation.
• Molecular Mechanisms of Cadmium-Induced Fibroblast Growth Factor 23 Upregulation in Osteoblast-Like Cells

  Shinsuke Kido; Marina Fujihara; Kengo Nomura; Shohei Sasaki; Rie Mukai; Ritsuko Ohnishi; Ichiro Kaneko; Hiroko Segawa; Sawako Tatsumi; Hiroto Izumi; Kimitoshi Kohno; Ken-ichi Miyamoto

  TOXICOLOGICAL SCIENCES OXFORD UNIV PRESS 139 (2) 301 - 316 1096-6080 2014/06 [Refereed]
   

  Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. Renal proximal tubules are a major target of Cd toxicity. The whole mechanism of the adverse effects of Cd remains unresolved, especially how renal damage is related to the development of bone lesions. Fibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic factor that regulates vitamin D and inorganic phosphate metabolism in the kidney. To clarify the role of FGF23 on Cd toxicity, we investigated the mechanisms of Cd-induced FGF23 production in the bone. Cd injection into mice significantly increased plasma FGF23 concentrations, but did not change FGF23 mRNA expression in bone. GalNAc-T3 is involved in secreting intact FGF23. To determine potential roles of GalNAc-T3 in Cd-induced FGF23 production, we examined the effect of Cd on GalNAc-T3 mRNA expression in vivo and in vitro. GalNAc-T3 gene expression was significantly increased in the bones of Cd-injected mice. Cd also enhanced the expression of GalNAc-T3 in cultured osteosarcoma UMR106 cells and primary osteocytes. Cd activated aryl hydrocarbon receptors (AhR) and AhR were required for GalNAc-T3 gene expression induced by Cd. In addition, Cd-dependent FGF23 production was completely inhibited by an AhR antagonist. AhR siRNA markedly suppressed the stimulation of transcriptional activity by Cd. Furthermore, Cd induced AhR activation via phosphorylation of Ser-68 by p38 kinase in the nuclear export signal of AhR. Thus, Cd stimulated GalNAc-T3 gene transcription via enhanced AhR binding to the GalNAc-T3 promoter. These findings suggest that the Cd-induced increase in GalNAc-T3 suppresses proteolytic processing of FGF23 and increases serum FGF23 concentrations.
• Hepatectomy-Related Hypophosphatemia: A Novel Phosphaturic Factor in the Liver-Kidney Axis

  Kengo Nomura; Sawako Tatsumi; Atsumi Miyagawa; Yuji Shiozaki; Shohei Sasaki; Ichiro Kaneko; Mikiko Ito; Shinsuke Kido; Hiroko Segawa; Mitsue Sano; Tsutomu Fukuwatari; Katsumi Shibata; Ken-ichi Miyamoto

  JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY AMER SOC NEPHROLOGY 25 (4) 761 - 772 1046-6673 2014/04 [Refereed]
   

  Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na+-dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na+-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.
• Activating transcription factor 4, an ER stress mediator, is required for, but excessive ER stress suppresses osteoblastogenesis by bortezomib

  Shingen Nakamura; Hirokazu Miki; Shinsuke Kido; Ayako Nakano; Masahiro Hiasa; Asuka Oda; Hiroe Amou; Keiichiro Watanabe; Takeshi Harada; Shiro Fujii; Kyoko Takeuchi; Kumiko Kagawa; Shuji Ozaki; Toshio Matsumoto; Masahiro Abe

  INTERNATIONAL JOURNAL OF HEMATOLOGY SPRINGER JAPAN KK 98 (1) 66 - 73 0925-5710 2013/07 [Refereed]
   

  Endoplasmic reticulum (ER) stress is induced in matrix-producing osteoblasts and plays an essential role in osteoblastogenesis. Although the bone anabolic activity of proteasome inhibitors has been demonstrated, the roles of ER stress induced by proteasome inhibition in osteoblastogenesis remain largely unknown. Here we show that bortezomib translationally increases protein levels of activating transcription factor 4 (ATF4), a downstream mediator of ER stress, in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells. The suppression of ATF4 expression by siRNA abrogated osteocalcin expression and mineralized nodule formation by MC3T3-E1 cells induced by bortezomib, indicating a critical role for ATF4 in bortezomib-mediated osteoblastogenesis. However, bortezomib at 20 nM or higher abolished the mineralized nodule formation along with reductions in the expression of osteoblastogenesis mediators beta-catenin and Osterix. Furthermore, at 50 nM, bortezomib induced the expression of C/EBP homologous protein (CHOP), suggesting activation of the ATF4-CHOP pro-apoptotic pathway. These results suggest that a low dose of bortezomib induces osteogenic activity, but that, in contrast, excessive ER stress caused by bortezomib at higher doses hampers osteoblastogenesis. Therefore, dosing schedules for proteasome inhibitors warrant further study to maximize anabolic actions without compromising anti-MM activity in patients with multiple myeloma (MM).
• Activating transcription factor 4, an ER stress mediator, is required for, but excessive ER stress suppresses osteoblastogenesis by bortezomib

  Shingen Nakamura; Hirokazu Miki; Shinsuke Kido; Ayako Nakano; Masahiro Hiasa; Asuka Oda; Hiroe Amou; Keiichiro Watanabe; Takeshi Harada; Shiro Fujii; Kyoko Takeuchi; Kumiko Kagawa; Shuji Ozaki; Toshio Matsumoto; Masahiro Abe

  International Journal of Hematology 98 (1) 66 - 73 0925-5710 2013/07 [Refereed]
   

  Endoplasmic reticulum (ER) stress is induced in matrix-producing osteoblasts and plays an essential role in osteoblastogenesis. Although the bone anabolic activity of proteasome inhibitors has been demonstrated, the roles of ER stress induced by proteasome inhibition in osteoblastogenesis remain largely unknown. Here we show that bortezomib translationally increases protein levels of activating transcription factor 4 (ATF4), a downstream mediator of ER stress, in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells. The suppression of ATF4 expression by siRNA abrogated osteocalcin expression and mineralized nodule formation by MC3T3-E1 cells induced by bortezomib, indicating a critical role for ATF4 in bortezomib-mediated osteoblastogenesis. However, bortezomib at 20 nM or higher abolished the mineralized nodule formation along with reductions in the expression of osteoblastogenesis mediators β-catenin and Osterix. Furthermore, at 50 nM, bortezomib induced the expression of C/EBP homologous protein (CHOP), suggesting activation of the ATF4-CHOP pro-apoptotic pathway. These results suggest that a low dose of bortezomib induces osteogenic activity, but that, in contrast, excessive ER stress caused by bortezomib at higher doses hampers osteoblastogenesis. Therefore, dosing schedules for proteasome inhibitors warrant further study to maximize anabolic actions without compromising anti-MM activity in patients with multiple myeloma (MM). © 2013 The Japanese Society of Hematology.
• Parathyroid Hormone (1-34) Counteracts the Suppression of Interleukin-11 Expression by Glucocorticoid in Murine Osteoblasts: A Possible Mechanism for Stimulating Osteoblast Differentiation Against Glucocorticoid Excess

  Rika Kuriwaka-Kido; Shinsuke Kido; Yuka Miyatani; Yuji Ito; Takeshi Kondo; Takashi Omatsu; Bingzi Dong; Itsuro Endo; Ken-ichi Miyamoto; Toshio Matsumoto

  ENDOCRINOLOGY ENDOCRINE SOC 154 (3) 1156 - 1167 0013-7227 2013/03 [Refereed]
   

  Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation. Intermittent PTH(1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess. We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of Delta FosB expression and protein kinase C (PKC)-delta-mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1. Because IL-11 suppresses the expression of dickkopf-1 and -2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation. The present study was undertaken to examine the effect of PTH(1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs). PTH(1-34) treatment of mPOBs enhanced IL-11 expression in a time-and dose-dependent manner. PTH(1-34) also stimulated Delta FosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription. PTH(1-34)-induced Smad1 phosphorylation was mediated via PKC delta and was abrogated in mPOBs from PKC delta knockout mice. Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting Delta FosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with Delta FosB. High doses of PTH(1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA. These results demonstrate that PTH(1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH(1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression. (Endocrinology 154: 1156-1167, 2013)
• Vitamin D and Type II Sodium-Dependent Phosphate Cotransporters

  Shinsuke Kido; Ichiro Kaneko; Sawako Tatsumi; Hiroko Segawa; Ken-ichi Miyamoto

  PHOSPHATE AND VITAMIN D IN CHRONIC KIDNEY DISEASE KARGER 180 86 - 97 0302-5144 2013 [Refereed]
   

  The type II sodium-dependent Pi (NaPi) cotransporters (NaPi-IIa, NaPi-IIb and NaPi-IIc) contribute to renal and intestinal Pi absorption. 1,25-Dihydroxyvitamin D [1,25(OH)(2)D-3] is an important factor for NaPi-II transporters in the small intestine and kidney. In a previous study, low levels of 1,25(OH)(2)D-3 appeared to suppress the expression of renal NaPi cotransporters. We identified a functional vitamin D receptor-responsive element in the human NaPi-IIa and NaPi-lIc genes in renal epithelial cells. In an analysis of vitamin D receptor (VDR)-null mice, we observed early onset of hypophosphatemia. The cause of the hypophosphatemia in VDR-null mice before weaning appeared to be increased plasma parathyroid hormone (PTH) levels during the suckling periods. A rescue diet (high calcium diet) decreased plasma PTH levels in VDR-null mice. The reduced plasma PTH levels normalized the renal Npt2a and Npt2c protein levels in weanling animals. Thus, the dietary intervention completely normalized the expression of the renal Pi transporters (Npt2a/Npt2c) in VDR-null mice, suggesting that the lack of VDR activity was not the cause of the impaired renal Pi reabsorption. In suckling animals, 1,25(OH)(2)D-3 may be essential for the prevention of the phosphaturic action of PTH. In adult animals, 1,25(OH)(2)D-3 is thought to be an important factor for posttranscriptional regulation of the Npt2b gene in the small intestine. Fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor that influences vitamin D metabolism and renal reabsorption of Pi. We characterized the role of the VDR in the action of FGF23 using VDR-null mice. FGF23 reduced renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that was independent of the VDR. By contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction in serum 1,25(OH)(2)D-3 levels induced by FGF23 were dependent on the VDR. Thus, the VDR is not essential for the phosphaturic action of FGF23, but is essential for control of the plasma 1,25(OH)(2)D-3 level. Moreover, FGF23 reduces intestinal NaPi transport activity and Npt2b protein levels by a mechanism that is dependent on the VDR. Klotho functions as a co-receptor for FGF23 and is increased by 1,25(OH)(2)D-3. Klotho induces phosphaturia by inhibiting the renal NaPi-Ila transporter. In this review, we discuss the roles of 1,25(OH)(2)D-3/VDR in the regulation of renal type II NaPi cotransporters in the kidney and small intestine. Copyright (C) 2013 S. Karger AG, Basel
• [Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium].

  Kido S; Fujihara M; Nomura K; Sasaki S; Shiozaki Y; Segawa H; Tatsumi S; Miyamoto K

  Nihon eiseigaku zasshi. Japanese journal of hygiene 4 67 (4) 464 - 471 0021-5082 2012/09 [Refereed]
   

  Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. Fibroblast growth factor 23 (FGF23) serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into C57BL/6J mice, plasma FGF23 concentration significantly increased. The urinary Pi excretion level was significantly higher in the Cd-injected C57BL/6J mice than in the control group. Plasma Pi concentration decreased only slightly in the Cd-injected mice compared with the control group. No changes were observed in the concentration of the plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both groups of mice. We observed a decrease in phosphate transport activity and also a decrease in the expression level of renal phosphate transporter Npt2c, but not that of Npt2a. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice, which expresses Npt2c as a major NaPi cotransporter. Injecting Cd to Npt2aKO mice induced a significant increase in plasma FGF23 concentration and urinary Pi excretion level. Furthermore, we observed decreases in phosphate transport activity and renal Npt2c expression level in the Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with FGF23.
• Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria

  Sakiko Haito-Sugino; Mikiko Ito; Akiko Ohi; Yuji Shiozaki; Natsumi Kangawa; Takashi Nishiyama; Fumito Aranami; Shohei Sasaki; Ayaka Mori; Shinsuke Kido; Sawako Tatsumi; Hiroko Segawa; Ken-ichi Miyamoto

  AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY AMER PHYSIOLOGICAL SOC 302 (9) C1316 - C1330 0363-6143 2012/05 [Refereed]
   

  Haito-Sugino S, Ito M, Ohi A, Shiozaki Y, Kangawa N, Nishiyama T, Aranami F, Sasaki S, Mori A, Kido S, Tatsumi S, Segawa H, Miyamoto K. Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria. Am J Physiol Cell Physiol 302: C1316-C1330, 2012. First published December 7, 2012; doi:10.1152/ajpcell.00314.2011.-Mutations in the apically located Na+-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c. 228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the V-max for P-i, but not the K-m. G196R, R468W, and c. 228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c. 228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability.
• Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling

  Toshio Matsumoto; Rika Kuriwaka-Kido; Takeshi Kondo; Itsuro Endo; Shinsuke Kido

  ENDOCRINE JOURNAL JAPAN ENDOCRINE SOC 59 (2) 91 - 101 0918-8959 2012/02 [Refereed]
   

  Mechanical stress and parathyroid hormone (PTH) are major stimulators, and aging and glucocorticoids excess are important suppressors of osteoblast differentiation. Mechanical stress and PTH stimulate interleukin (IL)-11 expression in cells of osteoblast lineage by enhancing transcription of IL-11 gene via an increase in intracellular Ca2+. The elevated Ca2+ activates extracellular signal-regulated kinase (ERK) to enhance phosphorylation of cyclic AMP response element-binding protein (CREB), which binds to the fosB gene promoter and enhances Delta FosB expression. Delta FosB dimerizes with JunD on the IL-11 gene promoter to enhance its transcription. Both mechanical stress and PTH also stimulate phosphorylation of Smad1 via an activation of protein kinase C delta (PKC delta). Phosphorylated Smad1 binds to the IL-11 gene promoter and forms complex with Delta FosB/JunD to further enhance IL-11 gene transcription. The increased IL-11 then suppresses expression of Wnt inhibitors, including Dickkopf 1 (Dkk1) and 2, and enhances Wnt signaling to stimulate osteoblast differentiation and inhibit adipocyte differentiation. The suppression of osteoblast differentiation by aging involves a decrease in IL-11 gene transcription by a reduction in JunD binding to the activator protein (AP)-1 site of the IL-11 gene promoter. Glucocorticoids inhibit transcriptional activation of IL-11 gene by an interaction of glucocorticoid-glucocorticoid receptor (GR) complex with Delta FosB/JunD heterodimer. Thus, factors that enhance osteoblast differentiation stimulate, and those which suppress osteoblast differentiation inhibit IL-11 gene transcription, and IL-11 enhances Writ signaling by suppressing expression of its inhibitors. These observations are consistent with the notion that IL-11 mediates stimulatory and inhibitory signals of osteoblast differentiation by affecting Wnt signaling.
• Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c

  Shoji Kuwahara; Fumito Aranami; Hiroko Segawa; Akemi Onitsuka; Naoko Honda; Rieko Tominaga; Etsuyo Hanabusa; Ichiro Kaneko; Setsuko Yamanaka; Shohei Sasaki; Akiko Ohi; Kengo Nomura; Sawako Tatsumi; Shinsuke Kido; Mikiko Ito; Ken-Ichi Miyamoto

  Journal of Medical Investigation 1-2 59 (1-2) 116 - 126 1343-1420 2012/02 [Refereed]
   

  Mutations in the SLC34A3 gene, a sodium-dependent inorganic phosphate (Pi) cotransporter, also referred to as NaPi IIc, causes hereditary hypophosphatemic rickets with hypercalciuria (HHRH), an autosomal recessive disorder. In human and rodent, NaPi IIc is mainly localized in the apical membrane of renal proximal tubular cells. In this study, we identified mouse NaPi IIc variant (Npt2c-v1) that lacks the part of the exon 3 sequence that includes the assumed translation initiation site of Npt2c. Microinjection of mouse Npt2c-v1 cRNA into Xenopus oocytes demonstrated that Npt2c-v1 showed sodium-dependent Pi cotransport activity. The characterization of pH dependency showed activation at extracellular alkaline-pH. Furthermore, Npt2c-v1 mediated Pi transport activity was significantly higher at any pH value than those of Npt2c. In an in vitro study, the localization of the Npt2c-v1 protein was detected in the apical membrane in opossum kidney cells. The expression of Npt2c-v1 mRNA was detected in the heart, spleen, testis, uterus, placenta, femur, cerebellum, hippocampus, diencephalon and brain stem of mouse. Using mouse bone primary cultured cells, we showed the expression of Npt2c-v1 mRNA. In addition, the Npt2c protein was detected in the spermatozoa head. Thus, Npt2c-v1 was expressed in extra-renal tissues such as epididymal spermatozoa and may function as a sodium-dependent phosphate transporter.
• Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b(+/-) mice

  Akiko Ohi; Etsuyo Hanabusa; Otoya Ueda; Hiroko Segawa; Naoshi Horiba; Ichiro Kaneko; Shoji Kuwahara; Tomo Mukai; Shohei Sasaki; Rieko Tominaga; Junya Furutani; Fumito Aranami; Shuichi Ohtomo; Yumiko Oikawa; Yousuke Kawase; Naoko A. Wada; Takanori Tachibe; Mami Kakefuda; Hiromi Tateishi; Kaoru Matsumoto; Sawako Tatsumi; Shinsuke Kido; Naoshi Fukushima; Kou-ichi Jishage; Ken-ichi Miyamoto

  AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY AMER PHYSIOLOGICAL SOC 301 (5) F1105 - F1113 1931-857X 2011/11 [Refereed]
   

  Ohi A, Hanabusa E, Ueda O, Segawa H, Horiba N, Kaneko I, Kuwahara S, Mukai T, Sasaki S, Tominaga R, Furutani J, Aranami F, Ohtomo S, Oikawa Y, Kawase Y, Wada NA, Tachibe T, Kakefuda M, Tateishi H, Matsumoto K, Tatsumi S, Kido S, Fukushima N, Jishage K, Miyamoto K. Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b(+/-) mice. Am J Physiol Renal Physiol 301: F1105-F1113, 2011. First published August 3, 2011; doi:10.1152/ajprenal.00663.2010.-An inorganic phosphate (P-i)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P-i (Na/P-i) transport system is involved in intestinal P-i absorption and is regulated by several factors. The type II sodium-dependent P-i transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P-i. In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P-i excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D-3 levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P-i cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma Pi levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na+/P-i transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.
• Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter npt2b +/-mice

  Akiko Ohi; Etsuyo Hanabusa; Otoya Ueda; Hiroko Segawa; Naoshi Horiba; Ichiro Kaneko; Shoji Kuwahara; Tomo Mukai; Shohei Sasaki; Rieko Tominaga; Junya Furutani; Fumito Aranami; Shuichi Ohtomo; Yumiko Oikawa; Yousuke Kawase; Naoko A. Wada; Takanori Tachibe; Mami Kakefuda; Hiromi Tateishi; Kaoru Matsumoto; Sawako Tatsumi; Shinsuke Kido; Naoshi Fukushima; Kou-ichi Jishage; Ken-ichi Miyamoto

  American Journal of Physiology - Renal Physiology 301 (5) F1105 - F1113 0363-6127 2011/11 [Refereed]
   

  An inorganic phosphate (P i)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P i (Na/P i) transport system is involved in intestinal Pi absorption and is regulated by several factors. The type II sodium-dependent P i transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports Pi. In the present study, we analyzed the phenotype of Npt2b -/-and hetero +/-mice. Npt2b -/-mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b +/-mice showed hypophosphatemia and low urinary Pi excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)2D3 levels were significantly increased in Npt2b +/-mice compared with Npt2b +/+ mice. Npt2b mRNA levels were reduced to 50% that in Npt2b +/+ mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b +/-mice. At 20 wk of age, Npt2b +/-mice showed hypophosphaturia and reduced Na/P i cotransport activity in the distal intestine. Npt2b +/+ mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b +/-mice treated with adenine had significantly reduced plasma Pi levels compared with Npt2b +/-mice. Intestinal Npt2b protein and Na +/P i transport activity levels were significantly lower in Npt2b +/-mice than in the Npt2b +/+ mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia. © 2011 the American Physiological Society.
• Sodium-Dependent Phosphate Cotransporters: Lessons from Gene Knockout and Mutation Studies

  Ken-Ichi Miyamoto; Sakiko Haito-Sugino; Shoji Kuwahara; Akiko Ohi; Kengo Nomura; Mikiko Ito; Masashi Kuwahata; Shinsuke Kido; Sawako Tatsumi; Ichiro Kaneko; Hiroko Segawa

  JOURNAL OF PHARMACEUTICAL SCIENCES WILEY 100 (9) 3719 - 3730 0022-3549 2011/09 [Refereed]
   

  Inorganic phosphate (Pi) is an essential physiological compound, highlighted by the syndromes caused by hypo or hyperphosphatemic states. Hyperphosphatemia is associated with ectopic calcification, cardiovascular disease, and increased mortality in patients with chronic kidney disease (CKD). As phosphate control is not efficient with diet or dialysis, oral Pi binders are used in over 90% of patients with renal failure. However, achieving tight control of serum Pi is difficult, and lower levels of serum Pi (severe hypophosphatemia) do not lead to better outcomes. The inhibition of sodium-dependent Pi (NaPi) transporter would be a preferable method to control serum Pi levels in patients with CKD or patients undergoing dialysis. Three types of NaPi transporters (types I-III) have been identified: solute carrier series SLC17A1 (NPT1/NaPi-I/OATv1), SLC34 (NaPi-IIa, NaPi-IIb, NaPi-IIc), and SLC20 (PiT1, PiT2), respectively. Knockout mice have been created for types I-III NaPi transporters. In this review, we discuss the roles of the NaPi transporters in Pi homeostasis. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3719-3730, 2011
• Mechanosensing and signaling crosstalks

  Toshio Matsumoto; Rika Kuriwaka-Kido; Shinsuke Kido

  Mechanosensing Biology Springer Japan 157 - 166 2011 [Refereed]
   

  Mechanical loading to bone causes mainly two types of stress to bone forming cells, fluid shear stress (FSS) and tensile stress. FSS appears to be a major stress signal that activates osteoblastic/osteocytic intracellular signaling to enhance bone formation. FSS to osteoblasts causes Ca2+ influx by activating a stress-activated cation channel, which activates extracellular signal-regulated kinase (ERK) to the phosphorylate cyclic AMP response element-binding protein (CREB). Phosphorylated CREB binds to the fosB gene promoter to enhance its transcriptional activity, and upregulates the expression of mainly ΔFosB, a C-terminal truncated splice variant of FosB. The increased ΔFosB binds to the 5′AP-1 site on the IL-11 gene promoter and forms a complex with JunD. FSS to osteoblasts also stimulates tyrosine phosphorylation of protein kinase Cδ (PKCδ), which activates Smad1/5. Activated Smad1/5 is bound to the Smad-binding element of the IL-11 gene promoter, and forms a complex with ΔFosB/JunD heterodimer. Thus, Ca2+-ERK-CREB-ΔFosB and PKCδ-Smad1/5 pathways merge together on the IL-11 gene promoter, and the two pathways cooperatively stimulate IL-11 gene expression in response to mechanical stress. The increase in interleukin (IL)-11 then enhances Wnt/β-catenin signaling by suppressing the expression of its inhibitors, dickkopf 1 and 2, in osteoblasts. Thus, the enhanced IL-11 expression by the cooperative AP-1 and Smad1/5 pathways is the upstream signal for stimulation of the main osteogenic pathway, Wnt/β-catenin signaling.
• Induction of endosomal/lysosomal pathways in differentiating osteoblasts as revealed by combined proteomic and transcriptomic analyses

  Takako Taniguchi; Shinsuke Kido; Emiko Yamauchi; Masahiro Abe; Toshio Matsumoto; Hisaaki Taniguchi

  FEBS LETTERS ELSEVIER SCIENCE BV 584 (18) 3969 - 3974 0014-5793 2010/09 [Refereed]
   

  We have analyzed proteome changes associated with bone-forming osteoblast differentiation by quantitative differential proteomic and transcriptomic analyses using in vitro differentiation model. Sixty nine proteins were found up-regulated (>2-fold) and 18 were down-regulated (<0.5-fold) at protein level. The mRNA levels of these proteins were then analyzed by quantitative real-time PCR combined with clustering analysis. The most prominent cluster with increased protein and mRNA levels contains endosomal and lysosomal proteins, demonstrating the drastic induction of degradative endosomal/lysosomal pathways in osteoblasts. Osteoblasts, therefore, are involved not only in the synthesis but also in the turnover of the extracellular matrix proteins such as collagens. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
• Mechanical Stress Activates Smad Pathway through PKC delta to Enhance Interleukin-11 Gene Transcription in Osteoblasts

  Shinsuke Kido; Rika Kuriwaka-Kido; Yuka Umino-Miyatani; Itsuro Endo; Daisuke Inoue; Hisaaki Taniguchi; Yasumichi Inoue; Takeshi Imamura; Toshio Matsumoto

  PLOS ONE PUBLIC LIBRARY SCIENCE 5 (9) 1932-6203 2010/09 [Refereed]
   

  Background: Mechanical stress rapidly induces Delta FosB expression in osteoblasts, which binds to interleukin (IL)-11 gene promoter to enhance IL-11 expression, and IL-11 enhances osteoblast differentiation. Because bone morphogenetic proteins (BMPs) also stimulate IL-11 expression in osteoblasts, there is a possibility that BMP-Smad signaling is involved in the enhancement of osteoblast differentiation by mechanical stress. The present study was undertaken to clarify whether mechanical stress affects BMP-Smad signaling, and if so, to elucidate the role of Smad signaling in mechanical stress-induced enhancement of IL-11 gene transcription. Methodology/Principal Findings: Mechanical loading by fluid shear stress (FSS) induced phosphorylation of BMP-specific receptor-regulated Smads (BR-Smads), Smad1/5, in murine primary osteoblasts (mPOBs). FSS rapidly phosphorylated Y311 of protein kinase C (PKC)delta, and phosphorylated PKC delta interacted with BR-Smads to phosphorylate BR-Smads. Transfection of PKC delta siRNA or Y311F mutant PKC delta abrogated BR-Smads phosphorylation and suppressed IL-11 gene transcription enhanced by FSS. Activated BR-Smads bound to the Smad-binding element (SBE) of IL-11 gene promoter and formed complex with Delta FosB/JunD heterodimer via binding to the C-terminal region of JunD. Site-directed mutagenesis in the SBE and the AP-1 site revealed that both SBE and AP-1 sites were required for full activation of IL-11 gene promoter by FSS. Conclusions/Significance: These results demonstrate that PKC delta-BR-Smads pathway plays an important role in the intracellular signaling in response to mechanical stress, and that a cross-talk between PKC delta-BR-Smads and Delta FosB/JunD pathways synergistically stimulates IL-11 gene transcription in response to mechanical stress.
• 新規リン利尿因子の探索

  野村 憲吾; 辰巳 佐和子; 菊井 聡子; 齋藤 友紀子; 塩崎 雄治; 山口 誠一; 木戸 慎介; 宮本 賢一

  日本栄養・食糧学会大会講演要旨集 (公社)日本栄養・食糧学会 64回 105 - 105 2010/05
• TGF-beta Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth

  Kyoko Takeuchi; Masahiro Abe; Masahiro Hiasa; Asuka Oda; Hiroe Amou; Shinsuke Kido; Takeshi Harada; Osamu Tanaka; Hirokazu Miki; Shingen Nakamura; Ayako Nakano; Kumiko Kagawa; Kenichiro Yata; Shuji Ozaki; Toshio Matsumoto

  PLOS ONE PUBLIC LIBRARY SCIENCE 5 (3) e9870  1932-6203 2010/03 [Refereed]
   

  Background: Multiple myeloma (MM) expands almost exclusively in the bone marrow and generates devastating bone lesions, in which bone formation is impaired and osteoclastic bone resorption is enhanced. TGF-beta, a potent inhibitor of terminal osteoblast (OB) differentiation, is abundantly deposited in the bone matrix, and released and activated by the enhanced bone resorption in MM. The present study was therefore undertaken to clarify the role of TGF-beta and its inhibition in bone formation and tumor growth in MM. Methodology/Principal Findings: TGF-beta suppressed OB differentiation from bone marrow stromal cells and MC3T3-E1 preosteoblastic cells, and also inhibited adipogenesis from C3H10T1/2 immature mesenchymal cells, suggesting differentiation arrest by TGF-beta. Inhibitors for a TGF-beta type I receptor kinase, SB431542 and Ki26894, potently enhanced OB differentiation from bone marrow stromal cells as well as MC3T3-E1 cells. The TGF-beta inhibition was able to restore OB differentiation suppressed by MM cell conditioned medium as well as bone marrow plasma from MM patients. Interestingly, TGF-beta inhibition expedited OB differentiation in parallel with suppression of MM cell growth. The anti-MM activity was elaborated exclusively by terminally differentiated OBs, which potentiated the cytotoxic effects of melphalan and dexamethasone on MM cells. Furthermore, TGF-beta inhibition was able to suppress MM cell growth within the bone marrow while preventing bone destruction in MM-bearing animal models. Conclusions/Significance: The present study demonstrates that TGF-beta inhibition releases stromal cells from their differentiation arrest by MM and facilitates the formation of terminally differentiated OBs, and that terminally differentiated OBs inhibit MM cell growth and survival and enhance the susceptibility of MM cells to anti-MM agents to overcome the drug resistance mediated by stromal cells. Therefore, TGF-beta appears to be an important therapeutic target in MM bone lesions.
• Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium

  Fumito Aranami; Hiroko Segawa; Junya Furutani; Shoji Kuwahara; Rieko Tominaga; Etsuyo Hanabusa; Sawako Tatsumi; Shinsuke Kido; Mikiko Ito; Ken-Ichi Miyamoto

  Journal of Medical Investigation 1-2 57 (1-2) 95 - 108 1343-1420 2010/02 [Refereed]
   

  Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D3 in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis.
• Mechanical stress induces Interleukin-11 expression to stimulate osteoblast differentiation

  Shinsuke Kido; Rika Kuriwaka-Kido; Takeshi Imamura; Yuji Ito; Daisuke Inoue; Toshio Matsumoto

  BONE ELSEVIER SCIENCE INC 45 (6) 1125 - 1132 8756-3282 2009/12 [Refereed]
   

  Molecular mechanism of mechanical stress-induced bone formation remains unclear. We demonstrate that mechanical unloading suppresses and reloading enhances Interleukin (IL)-11 gene expression in the hindlimb of mice in vivo. Mechanical stress to osteoblasts by fluid shear stress (FSS) in vitro rapidly and transiently enhances fosB gene transcription, stimulates binding of Delta FosB/JunD complex to activator protein (AP)-1 site of the IL-11 gene promoter, and enhances IL-11 gene transcription. Anti-IL-11 antibody blocks mechanical stress-induced enhancement of osteoblastogenesis and suppression of adipogenesis, suggesting the requirement of IL-11 for the stimulation of osteoblast differentiation by mechanical stress. Downregulation of Delta FosB/JtmD by small interfering RNA (siRNA) suppresses and overexpression of Delta FosB/JunD enhances IL-11 gene promoter activity. Consistent with our previous observations that up-regulation of Delta FosB depends upon activation of cyclic AMP response element-binding protein (CREB) via Ca(2+)-dependent activation of extracellular signal-regulated kinase (ERK) to phosphorylate CREB, mechanical stress-induced activation of IL-11 gene transcription is dependent upon Ca(2+)-ERK pathway. Present results also demonstrated that FSS to osteoblasts enhances canonical Wnt signaling in vitro, and that mechanical unloading induces and reloading suppresses the expression of a canonical Wnt signal inhibitor, dickkopf2 (Dkk2), in vivo. In addition, IL-11 siRNA enhances Dkk2 expression suppressed by FSS, and osteoblasts from IL-11 transgenic mice show reduced Dkk2 mRNA expression than those from wild-type mice. These observations are consistent with the notion that mechanical stress stimulates IL-11 gene transcription via an enhanced OFosB/JunD binding to the IL-11 gene promoter, and that increased IL-11 enhances canonical Wnt signal at least in part via a reduction in Dkk2 expression to stimulate osteoblast differentiation. (C) 2009 Elsevier Inc. All rights reserved.
• シナカルセト塩酸塩によるリン管理

  菊井 聡子; 辰巳 佐和子; 野村 憲吾; 齋藤 友紀子; 塩崎 雄治; 山口 誠一; 木戸 慎介; 宮本 賢一

  日本病態栄養学会誌 (一社)日本病態栄養学会 12 (5) 181 - 181 1345-8167 2009/12
• GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme (TACE)

  Masahiro Hiasa; Masahiro Abe; Ayako Nakano; Asuka Oda; Hiroe Amou; Shinsuke Kido; Kyoko Takeuchi; Kumiko Kagawa; Kenichiro Yata; Toshihiro Hashimoto; Shuji Ozaki; Kenzo Asaoka; Eiji Tanaka; Keiji Moriyama; Toshio Matsumoto

  BLOOD AMER SOC HEMATOLOGY 114 (20) 4517 - 4526 0006-4971 2009/11 [Refereed]
   

  Monocytes give rise to macrophages, osteoclasts (OCs), and dendritic cells (DCs). Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB (RANK) ligand induce OC differentiation from monocytes, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) trigger monocytic differentiation into DCs. However, regulatory mechanisms for the polarization of monocytic differentiation are still unclear. The present study was undertaken to clarify the mechanism of triggering the deflection of OC and DC differentiation from monocytes. GM-CSF and IL-4 abolished monocytic differentiation into OCs while inducing DC differentiation even in the presence of M-CSF and RANK ligand. GM-CSF and IL-4 in combination potently up-regulate tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) and activity in monocytes, causing ectodomain shedding of M-CSF receptor, resulting in the disruption of its phosphorylation by M-CSF as well as the induction of osteoclastogenesis from monocytes by M-CSF and RANK ligand. Interestingly, TACE inhibition robustly causes the resumption of the surface expression of M-CSF receptor on monocytes, facilitating M-CSF-mediated phosphorylation of M-CSF receptor and macrophage/OC differentiation while impairing GM-CSF- and IL-4-mediated DC differentiation from monocytes. These results reveal a novel proteolytic regulation of M-CSF receptor expression in monocytes to control MCSF signaling and monocytic differentiation into macrophage/OC-lineage cells or DCs. (Blood. 2009;114:4517-4526)
• Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-1 alpha and MIP-1 beta production

  Masahiro Abe; Kenji Hiura; Shuji Ozaki; Shinsuke Kido; Toshio Matsumoto

  JOURNAL OF BONE AND MINERAL METABOLISM SPRINGER JAPAN KK 27 (1) 16 - 23 0914-8779 2009/01 [Refereed]
   

  Multiple myeloma (MM) cell adhesion to stromal cells via very late antigen (VLA)-4 and vascular cell adhesion molecule (VCAM)-1 interaction causes enhanced secretion of osteoclastogenic activity by MM cells. We have reported that MM cell-derived macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta are responsible for most of the osteoclastogenic activity in MM. Thus, adhesion-mediated osteoclastogenesis may be caused by enhanced production of MIP-1 via VLA-4-VCAM-1 interaction. The present study was undertaken to clarify whether MM cell-derived MIP-1 plays a role in VLA-4-VCAM-1 adhesion-mediated osteoclastogenesis. Adhesion of MM cells to VCAM-1 upregulated MIP-1 alpha and MIP-1 beta production from MM cells and enhanced production of osteoclastogenic activity by MM cells. Blockade of MIP-1 alpha and MIP-1 beta actions not only abrogated elaboration of osteoclastogenic activity, but also suppressed spontaneous MM cell adhesion to VCAM-1. These results demonstrate that MM cell adhesion to VCAM-1 upregulates MIP-1 production by MM cells to cause enhancement of osteoclastogenesis. In addition, the results suggest that the increased production of MIP-1 further enhances MM cell binding to stromal cells via stimulation of VLA-4-VCAM-1 adhesion, forming a "vicious cycle" between MM cell adhesion to stromal cells and MIP-1 production via VLA-4-VCAM-1 interaction.
• TACE up-regulation in monocytes by GM-CSF and IL-4 disrupts myeloma cell-induced osteoclastogenesis while inducing dendritic cell differentiation

  Masahiro Abe; Masahiro Hiasa; Shinsuke Kido; Asuka Oda; Hiroe Amou; Kyoko Takeuchi; Kenichiro Yata; Shuji Ozaki; Toshio Matsumoto

  CANCER TREATMENT REVIEWS ELSEVIER SCI LTD 34 S64 - S65 0305-7372 2008 [Refereed]
  
• TNFα converting enzyme(TACE)による破骨細胞・骨髄系樹状細胞分化の制御

  日浅 雅博; 安倍 正博; 橋本 年弘; 木戸 慎介; 竹内 恭子; 北添 健一; 浅野 仁; 尾崎 修治; 森山 啓司; 松本 俊夫

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 25回 233 - 233 1349-0761 2007/06 [Refereed]
  
• Myeloma cell-osteoclast interaction enhances angiogenesis together with bone resorption: A role for vascular endothelial cell growth factor and osteopontin

  Ybichi Tanaka; Masahiro Abe; Masahiro Hiasa; Asuka Oda; Hiroe Amou; Ayako Nakano; Kyoko Takeuchi; Kenichi Kitazoe; Shinsuke Kido; Daisuke Inoue; Keiji Moriyama; Toshihiro Hashimoto; Shuji Ozaki; Toshio Matsumoto

  CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 13 (3) 816 - 823 1078-0432 2007/02 [Refereed]
   

  Purpose: Similar to osteoclastogenesis, angiogenesis is enhanced in the bone marrow in myeloma in parallel with tumor progression. We showed previously that myeloma cells and osteoclasts are mutually stimulated to form a vicious cycle to lead to enhance both osteoclastogenesis and tumor growth. The present study was undertaken to clarify whether myeloma cell-osteoclast interaction enhances angiogenesis and whether there is any mutual stimulation between osteoclastogenesis and angiogenesis. Experimental Design: Myeloma cells and monocyte-derived osteoclasts were cocultured, and angiogenic activity produced by the cocultures was assessed with in vitro vascular tubule formation assays and human umbilical vascular endothelial cell (HUVEC) migration and survival. Osteoclastogenic activity was determined with rabbit bone cell cultures on dentine slices. Results: Myeloma cells and osteoclasts constitutively secrete proangiogenic factors, vascular endothelial growth factor (VEGF) and osteopontin, respectively. A cell-to-cell interaction between myeloma cells and osteoclasts potently enhanced vascular tubule formation. Blockade of both VEGF and osteopontin actions almost completely abrogated such vascular tubule formation as well as migration and survival of HUVECs enhanced by conditioned medium from cocultures of myeloma cells and osteoclasts. Furthermore, these factors in combination triggered the production of osteoclastogenic activity by HUVEC. Conclusions: Osteoclast-derived osteopontin and VEGF from myeloma cells cooperatively enhance angiogenesis and also induce osteoclastogenic activity by vascular endothelial cells. These observations suggest the presence of a close link between myeloma cells, osteoclasts, and vascular endothelial cells to form a vicious cycle between bone destruction, angiogenesis, and myeloma expansion.
• GM-CSFとIL-4は単球のM-CSF受容体のectodomain sheddingを介し破骨細胞分化を抑制し樹状細胞分化を誘導する

  日浅 雅博; 安倍 正博; 木戸 慎介; 長樂 雅仁; 浅野 仁; 賀川 久美子; 竹内 恭子; 北添 健一; 橋本 年弘; 尾崎 修治; 井上 大輔; 森山 啓司; 松本 俊夫

  臨床血液 (一社)日本血液学会-東京事務局 47 (9) 1150 - 1150 0485-1439 2006/09 [Refereed]
  
• BAFF and APRIL as osteoclast-derived survival factors for myeloma cells: a rationale for TACl-Fc treatment in patients with multiple myeloma

  M. Abe; S. Kido; M. Hiasa; A. Nakano; A. Oda; H. Amou; T. Matsumoto

  LEUKEMIA NATURE PUBLISHING GROUP 20 (7) 1313 - 1315 0887-6924 2006/07 [Refereed]
  
• GM-CSFとIL-4は単球のM-CSF受容体の切断を介し破骨細胞分化を抑制し樹状細胞分化を誘導する

  日浅 雅博; 安倍 正博; 橋本 年弘; 尾崎 修治; 井上 大輔; 木戸 慎介; 森山 啓司; 松本 俊夫

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 24回 206 - 206 1349-0761 2006/07 [Refereed]
  
• c-Fos degradation by the ubiquitin-proteasome proteolytic pathway in osteoclast progenitors

  Y Ito; D Inoue; S Kido; T Matsumoto

  BONE ELSEVIER SCIENCE INC 37 (6) 842 - 849 8756-3282 2005/12 [Refereed]
   

  c-Fos is an immediate early gene type proto-oncogene that belongs to the AP (activator protein)-1 transcription factor family. Gene knockout experiments have demonstrated that, among the Fos family, only c-Fos is indispensable for osteoclast differentiation but that c-Fos can be substituted for by other Fos family members including FosB/Delta FosB, Fra-1 and Fra-2, in most other tissues and cells. To further understand a unique role of c-Fos in osteoclastogenesis, we investigated the temporal profile and regulatory mode of expression of c-Fos during the course of osteoclast differentiation. The results indicated that c-Fos protein gradually increased in preosteoclasts during differentiation to a greater extent than that of mRNA induction. We then determined the proteolytic pathway of c-Fos conferring unstable nature on c-Fos protein in a preosteoclastic cell line, RAW264.7. Proteasome inhibitors including MG 132 and Z-LLF caused a rapid increase in c-Fos protein expression in these cells within several hours, but other inhibitors of cysteine protease (E-64), lysosome (chloroquine) and calpain (ALLM) did not. Moreover, the proteasome inhibitors caused an extensive accumulation of ubiquitinated c-Fos protein and an approximately three-fold extension of the c-Fos protein half-life. We therefore conclude that the ubiquitin-proteasome system is the major proteolytic pathway conferring instability on c-Fos protein in preosteoclasts. Our results further imply that c-Fos stabilization due to dynamic changes in the ubiquitin-proteasome-dependent degradation may be involved in the accumulation of c-Fos protein in differentiating preosteoclasts. (c) 2005 Elsevier Inc. All rights reserved.
• Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2

  T Oshima; M Abe; J Asano; T Hara; K Kitazoe; E Sekimoto; Y Tanaka; H Shibata; T Hashimoto; S Ozaki; S Kido; D Inoue; T Matsumoto

  BLOOD AMER SOC HEMATOLOGY 106 (9) 3160 - 3165 0006-4971 2005/11 [Refereed]
   

  Multiple myeloma (MM) develops devastating bone destruction with enhanced bone resorption and suppressed bone formation. In contrast to enhanced osteoclastogenesis, little is known about the mechanism of impaired bone formation in MM. Because a canonical Wingless-type (Wnt) signaling pathway has recently been shown to play an important role in osteoblast differentiation, we examined whether MM cells affect a canonical Wnt pathway to suppress bone formation. Conditioned media from RPM18226 and U266 MM cell lines and primary MM cells suppressed in vitro mineralization as well as alkaline phosphatase activity in osteoblasts induced by bone morphogenetic protein 2 (BMP-2). These cell lines constitutively produced a soluble Wnt inhibitor, secreted Frizzled-related protein 2 (sFRP-2), but not other Wnt inhibitors including sFRP-1, sFRP-3, and dickkopf 1 (DKK-1) at the protein level. Most MM cells from patients with advanced bone destructive lesions also expressed sFRP-2. Furthermore, exogenous sFRP-2 suppressed osteoblast differentiation induced by BMP-2, and immunodepletion of sFRP-2 significantly restored mineralized nodule formation in vitro, suggesting a predominant role for MM cell-derived sFRP-2 in the impairment of bone formation by MM. Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2.
• Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappa B ligand and vascular endothelial growth factor to enhance osteoclastogenesis

  H Shibata; M Abe; K Hiura; J Wilde; K Moriyama; T Sano; K Kitazoe; T Hashimoto; S Ozaki; S Wakatsuki; S Kido; D Inoue; T Matsumoto

  CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 11 (17) 6109 - 6115 1078-0432 2005/09 [Refereed]
   

  Purpose: Receptor activator of nuclear factor-kappa B ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. Experimental Design and Results: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte- derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell - derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. Conclusions: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.
• 骨髄腫細胞,破骨細胞と血管内皮細胞の細胞間相互作用

  田中 洋一; 安倍 正博; 日浅 雅博; 橋本 年弘; 木戸 慎介; 井上 大輔; 尾崎 修治; 森山 啓司; 松本 俊夫

  日本血液学会・日本臨床血液学会総会プログラム・抄録集 日本臨床血液学会 67回・47回 741 - 741 2005/09 [Refereed]
  
• 骨髄腫細胞,破骨細胞と血管内皮細胞の細胞間相互作用 腫瘍進展,骨破壊と血管新生の促進

  田中 洋一; 安倍 正博; 日浅 雅博; 橋本 年弘; 木戸 慎介; 井上 大輔; 尾崎 修治; 森山 啓司; 松本 俊夫

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 23回 164 - 164 1349-0761 2005/06 [Refereed]
  
• Transcriptional induction of FosB/Delta FosB gene by mechanical stress in osteoblasts

  D Inoue; S Kido; T Matsumoto

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 279 (48) 49795 - 49803 0021-9258 2004/11 [Refereed]
   

  Mechanical stress to bone plays a critical role in maintaining bone mass and strength. However, the molecular mechanism of mechanical stress-induced bone formation is not fully understood. In the present study, we demonstrate that FosB and its spliced variant DeltaFosB, which is known to increase bone mass by stimulating bone formation in vivo, is rapidly induced by mechanical loading in mouse hind limb bone in vivo and by fluid shear stress (FSS) in mouse calvarial osteoblasts in vitro both at the mRNA and protein levels. FSS induction of FosB/DeltaFosB gene expression was dependent on gadlinium-sensitive Ca2+ influx and subsequent activation of ERK1/2. Analysis of the mouse FosB/DeltaFosB gene upstream regulatory region with luciferase reporter gene assays revealed that the FosB/DeltaFosB induction by FSS occurred at the transcriptional level and was conferred by a short fragment from -603 to -327. DNA precipitation assays and DNA decoy experiments indicated that ERK-dependent activation of CREB binding to a CRE/AP-1 like element (designated "CRE2") at the position of -413 largely contributed to the transcriptional effects of FSS. These results suggest that DeltaFosB participates in mechanical stress-induced intracellular signaling cascades that activate the osteogenic program in osteoblasts.
• Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion

  M Abe; K Hiura; J Wilde; A Shioyasono; K Moriyama; T Hashimoto; S Kido; T Oshima; H Shibata; S Ozaki; D Inoue; T Matsumoto

  BLOOD AMER SOC HEMATOLOGY 104 (8) 2484 - 2491 0006-4971 2004/10 [Refereed]
   

  Multiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti-IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion. (C) 2004 by The American Society of Hematology.
• [fosB/IL-11].

  Kido S; Inoue D

  Nihon rinsho. Japanese journal of clinical medicine 62 Suppl 2 62 - 67 0047-1852 2004/02 [Refereed]
  
• Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice

  E Tohjima; D Inoue; N Yamamoto; S Kido; Y Ito; S Kato; Y Takeuchi; S Fukumoto; T Matsumoto

  JOURNAL OF BONE AND MINERAL RESEARCH AMER SOC BONE & MINERAL RES 18 (8) 1461 - 1470 0884-0431 2003/08 [Refereed]
   

  Expression of an osteogenic cytokine, IL-11, is decreased in SAMP6. We show here that IL-11 transcription largely depends on AP-1 transcription factors, activities of which are decreased in SAMP6 as well as aged ICR mice. Therefore, diminished AP-1 activity and the resultant decline in IL-11 expression may play a role in impaired bone formation in the aged. Introduction: Evidence suggests that impaired osteoblastogenesis contributes to aging-associated osteopenia. The P6 strain of senescence-accelerated mice (SAM) is an animal model of senile osteoporosis, which exhibits low bone mass caused by impaired bone formation. Bone marrow stromal cells from SAMP6 show decreased osteoblasto-genesis and increased adipogenesis. We previously demonstrated that these abnormalities of SAMP6 stromal cells may be attributed to decreased expression of interleukin (IL)-11. Methods: In this study, we attempted to determine the molecular mechanism of decreased IL-11 expression by SAMP6 stromal cells by cloning and analyzing the mouse IL-11 gene promoter. Results and Conclusions: We found that two tandem activating protein-1 (AP-1) sites that reside immediately upstream of TATA box play critical roles in IL-11 gene transcription. Gel shift analysis showed that binding activity to the IL-11 AP-1 sites was reduced in SAMP6 stromal cell nuclear extracts. Among multiple components of AP-1 transcription factors, Jun D binding was particularly decreased. Furthermore, decreased Jun D binding and IL-11 expression by stromal cells was also observed in aged mice of the ICR strain. Therefore, decreased AP-1 activity and a resultant decline in IL-11 expression by bone marrow stromal cells may play a role in impaired bone formation in the aged.
• Expression of RANK is dependent upon differentiation into the macrophage/osteoclast lineage: induction by 1 alpha,25-dihydroxyvitamin D-3 and TPA in a human myelomonocytic cell line, HL60

  S Kido; D Inoue; K Hiura; W Javier; Y Ito; T Matsumoto

  BONE ELSEVIER SCIENCE INC 32 (6) 621 - 629 8756-3282 2003/06 [Refereed]
   

  Receptor activator of nuclear factor (RANK) is a member of the tumor necrosis factor receptor superfamily indispensable for osteoclast differentiation. However. little is known about the regulatory mechanism of RANK expression. In the present study, RANK expression during macrophage/osteoclast differentiation was investigated using a human myelomonocytic cell line, HL60, capable of differentiating into mature osteoclasts under appropriate conditions. RANK mRNA expression was barely detectable in growing HL60 cells. We found that treatment with lalpha,25-dihydroxyvitamin D-3 and TPA resulted in an apparent induction of RANK mRNA and protein in association with differentiation into the macrophage/osteoclast lineage. Induction of RANK was time and dose dependent and lineage specific. Moreover, RANK induction was blocked by an RNA polymerase II inhibitor, suggesting an involvement of a transcriptional mechanism. The induced RANK was functional as it was able to bind RANK ligand and activate NF-kappaB. In the induced HL60 cells expressing both c-Fms and RANK, RANK mRNA expression was further enhanced by RANKL, but not by macrophage colony-stimulating factor. These results suggest a positive feedback regulation of RANK expression by its own intracellular signaling. The in vitro system described here may be a useful model to elucidate the regulatory mechanism of RANK expression and its role in human osteoclastogenesis. (C) 2003 Elsevier Science (USA). All rights reserved.
• Role for macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta in the development of osteolytic lesions in multiple myeloma

  M Abe; K Hiura; J Wilde; K Moriyama; T Hashimoto; S Ozaki; S Wakatsuki; M Kosaka; S Kido; D Inoue; T Matsumoto

  BLOOD AMER SOC HEMATOLOGY 100 (6) 2195 - 2202 0006-4971 2002/09 [Refereed]
   

  Multiple myeloma (MM) cells cause devastating bone destruction by activating osteoclasts in the bone marrow milieu. However, the mechanism of enhanced bone resorption in patients with myeloma is poorly understood. In the present study, we investigated a role of C-C chemokines, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, in MM cell-induced osteolysis. These chemokines were produced and secreted by a majority of MM cell lines as well as primary MM cells from patients. Secretion of MIP-1alpha and MIP-1beta correlated well with the ability of myeloma cells to enhance osteoclastic bone resorption both in vitro and in vivo as well as in MM patients. In osteoclastogenic cultures of rabbit bone cells, cocultures with myeloma cells as well as addition of myeloma cell-conditioned media enhanced both formation of osteoclastlike cells and resorption pits to an extent comparable to the effect of recombinant MIP-1alpha and MIP-1beta. Importantly, these effects were mostly reversed by neutralizing antibodies against MIP-1alpha and MIP-1beta, or their cognate receptor, CCR5, suggesting critical roles of these chemokines. We also demonstrated that stromal cells express CCR5 and that recombinant MIP-1alpha and MIP-1beta induce expression of receptor activator of nuclear factor-kappaB (RANK) ligand by stromal cells, thereby stimulating osteoclast differentiation of preosteoclastic cells. These results suggest that MIP-1alpha and MIP-1beta may be major osteoclast-activating factors produced by MM cells.
• Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta

  R Okazaki; D Inoue; M Shibata; M Saika; S Kido; H Ooka; H Tomiyama; Y Sakamoto; T Matsumoto

  ENDOCRINOLOGY ENDOCRINE SOC 143 (6) 2349 - 2356 0013-7227 2002/06 [Refereed]
   

  Although cells of the osteoblast lineage express functional ERs, direct effects of estrogen on bone formation remain obscure. In the present study, we have investigated estrogen effects on osteoblastic and adipocytic differentiation from a mouse bone marrow stromal cell line, ST-2, which had been manipulated to overexpress either human ERalpha (ST2ERalpha) or ERP (T2ERbeta). Treatment with bone morphogenetic protein-2 increased alkaline phosphatase activity as well as the number of Oil Red O-positive adipocytes, indicating that bone morphogenetic protein-2 stimulated both osteoblastic and adipocytic differentiation from these bipotential cells. In both ST2ERa and ST2ERbeta cells, cotreatment with E2 caused enhancement of alkaline phosphatase activity and suppression of lipid accumulation. These effects were completely reversed by an ER antagonist, ICI182780. Therefore, the estrogen regulation occurred in an ER-specific manner but without ER subtype specificity. Moreover, dose response curves of the opposing effects of estrogen on osteoblastogenesis and adipogenesis formed an apparent mirror image, consistent with a reciprocal regulation of differentiation into the two cell lineages. These results demonstrate that estrogen directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast. Such effects would lead to direct stimulation of bone formation and thereby contribute to the protective effects of estrogen on bone.
• Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta

  R Okazaki; D Inoue; M Shibata; M Saika; S Kido; H Ooka; H Tomiyama; Y Sakamoto; T Matsumoto

  ENDOCRINOLOGY ENDOCRINE SOC 143 (6) 2349 - 2356 0013-7227 2002/06 [Refereed]
   

  Although cells of the osteoblast lineage express functional ERs, direct effects of estrogen on bone formation remain obscure. In the present study, we have investigated estrogen effects on osteoblastic and adipocytic differentiation from a mouse bone marrow stromal cell line, ST-2, which had been manipulated to overexpress either human ERalpha (ST2ERalpha) or ERP (T2ERbeta). Treatment with bone morphogenetic protein-2 increased alkaline phosphatase activity as well as the number of Oil Red O-positive adipocytes, indicating that bone morphogenetic protein-2 stimulated both osteoblastic and adipocytic differentiation from these bipotential cells. In both ST2ERa and ST2ERbeta cells, cotreatment with E2 caused enhancement of alkaline phosphatase activity and suppression of lipid accumulation. These effects were completely reversed by an ER antagonist, ICI182780. Therefore, the estrogen regulation occurred in an ER-specific manner but without ER subtype specificity. Moreover, dose response curves of the opposing effects of estrogen on osteoblastogenesis and adipogenesis formed an apparent mirror image, consistent with a reciprocal regulation of differentiation into the two cell lineages. These results demonstrate that estrogen directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast. Such effects would lead to direct stimulation of bone formation and thereby contribute to the protective effects of estrogen on bone.
• 悪循環を形成する骨髄腫細胞と骨細胞間の相互作用(Interactions between myeloma cells and bone cells forming a vicious cycle)

  Abe Masahiro; Inoue Daisuke; Kido Shinsuke; Hiura Kenji; Moriyama Keiji; Hashimoto Toshihiro; Shibata Hironobu; Oshima Takashi; Ozaki Shuji; Kosaka Masaaki

  Journal of Bone and Mineral Metabolism (一社)日本骨代謝学会 19 (Suppl.) 62 - 62 0914-8779 2001/10 [Refereed]
  
• 間質細胞誘導因子(SDF)-1による骨向性と癌増殖および破骨細胞形成(Bone tropism and growth of cancers and osteoclastogenesis by stromal cell-derived factor (SDF)-1)

  Abe Masahiro; Hiura Kenji; Moriyama Keiji; Hashimoto Toshihiro; Shibata Hironobu; Oshima Takashi; Kido Shinsuke; Inoue Daisuke; Ozaki Shuji; Matsumoto Toshio

  Journal of Bone and Mineral Metabolism (一社)日本骨代謝学会 19 (Suppl.) 60 - 60 0914-8779 2001/10 [Refereed]
  
• 骨髄腫細胞との接触により破骨細胞はIL-6,オステオポンチンの産生増加を介して骨髄腫細胞の増殖を促進する

  安倍 正博; 日浦 賢治; Javier Wilde; 森山 啓司; 橋本 年弘; 木戸 慎介; 大島 隆志; 柴田 泰伸; 尾崎 修治; 井上 大輔

  日本骨代謝学会雑誌 (一社)日本骨代謝学会 19 (2) 70 - 70 0910-0067 2001/07 [Refereed]
  
• 17 beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha

  M Saika; D Inoue; S Kido; T Matsumoto

  ENDOCRINOLOGY ENDOCRINE SOC 142 (6) 2205 - 2212 0013-7227 2001/06 [Refereed]
   

  Osteoprotegerin (OPG) is a recently identified member of the tumor necrosis factor (TNF) receptor superfamily that regulates bone mass through an inhibitory action on osteoclast differentiation and function. To determine its potential roles of OPG in pathological changes in bone metabolism caused by estrogen deficiency, we investigated effects of estrogen on OPG expression by a mouse stromal cell line, ST-2, in vitro. Treatment of ST-2 cells with 17 beta -E-2 resulted in up-regulation of OPG expression at both the messenger RNA and protein levels. The effect was time and dose dependent and steroid specific. The stimulatory action of 17 beta -E-2 on OPG expression appeared to be mediated by the estrogen receptor-alpha (ER alpha) subtype because stable overexpression of ER alpha, but not of ER beta, enhanced the OPG induction by 17 beta -E-2. Moreover, estrogen withdrawal after 5-day pretreatment, mimicking the event occurring in vivo at menopause, dramatically diminished the expression of OPG. These findings suggest that down-regulation of OPG after estrogen withdrawal contributes to the enhanced osteoclastic bone resorption and bone loss after menopause by enhancing RANK ligand-RANK system that lies downstream of a large number of bone-resorbing cytokines.
• 破骨細胞との接触を介する骨髄腫細胞の増殖の促進

  安倍 正博; 日浦 賢治; Wilde Javier; 森山 啓司; 木戸 慎介; 井上 大輔; 松本 俊夫

  日本骨代謝学会雑誌 (一社)日本骨代謝学会 18 (2) 156 - 156 0910-0067 2000/06 [Refereed]
  
• Identification of regulatory sequences and binding proteins in the type II sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate

  S Kido; K Miyamoto; H Mizobuchi; Y Taketani; Ohkido, I; N Ogawa; Y Kaneko; S Harashima; E Takeda

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 274 (40) 28256 - 28263 0021-9258 1999/10 [Refereed]
   

  Dietary phosphate (P-i) is a most important regulator for renal P-i reabsorption. The type II sodium-dependent phosphate (Na/P-i) cotransporters (NPT2) are located at the apical membranes of renal proximal tubular cells and major functional transporters associated with renal P-i reabsorption. The consumption of a low-P-i diet induces the synthesis of NPT2, whereas a high P-i diet decreases it, The molecular mechanisms of regulation by dietary P-i are not yet known. In this report, in weaning mice fed a low-P-i diet for 4 days, the NPT2 mRNA level was increased 1.8-fold compared with mice fed a normal P-i diet. This increase was due to an elevation of the transcriptional activity. In the NPT2 gene promoter, the DNA footprint analysis showed that six regions were masked by the binding protein, but at the position -1010 to -985 upstream of the transcription start site, the binding clearly responded to the levels of dietary P-i, The phosphate response element (PRE) of the NPT2 gene was found to consist of the motif related to the E box, 5'-CACGTG-3'. A yeast one-hybrid system was used to clone a transcription factor that binds to the PRE sequences in the proximal promoter of the NPT2 gene. Two cDNA clones that encoded protein of the mouse transcription factor mu E3 (TFE3) were isolated. This is a DNA-binding protein that activates transcription through the mu E3 site of the immunoglobulin heavy chain enhancer. TFE3 antibody completely inhibited the binding to the PRE. The coexpression of TFE3 in COS-7 cells transfected with the NPT2 gene promoter markedly stimulated the transcriptional activity. The feeding of a low P-i diet significantly increased the amount of TFE3 mRNA in the kidney. These findings suggest that TFE3 may participate in the transcriptional regulation of the NPT2 gene by dietary P-i.
• Identification of regulatory sequences and binding proteins in the type II sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate

  S Kido; K Miyamoto; H Mizobuchi; Y Taketani; Ohkido, I; N Ogawa; Y Kaneko; S Harashima; E Takeda

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 274 (40) 28256 - 28263 0021-9258 1999/10 [Refereed]
   

  Dietary phosphate (P-i) is a most important regulator for renal P-i reabsorption. The type II sodium-dependent phosphate (Na/P-i) cotransporters (NPT2) are located at the apical membranes of renal proximal tubular cells and major functional transporters associated with renal P-i reabsorption. The consumption of a low-P-i diet induces the synthesis of NPT2, whereas a high P-i diet decreases it, The molecular mechanisms of regulation by dietary P-i are not yet known. In this report, in weaning mice fed a low-P-i diet for 4 days, the NPT2 mRNA level was increased 1.8-fold compared with mice fed a normal P-i diet. This increase was due to an elevation of the transcriptional activity. In the NPT2 gene promoter, the DNA footprint analysis showed that six regions were masked by the binding protein, but at the position -1010 to -985 upstream of the transcription start site, the binding clearly responded to the levels of dietary P-i, The phosphate response element (PRE) of the NPT2 gene was found to consist of the motif related to the E box, 5'-CACGTG-3'. A yeast one-hybrid system was used to clone a transcription factor that binds to the PRE sequences in the proximal promoter of the NPT2 gene. Two cDNA clones that encoded protein of the mouse transcription factor mu E3 (TFE3) were isolated. This is a DNA-binding protein that activates transcription through the mu E3 site of the immunoglobulin heavy chain enhancer. TFE3 antibody completely inhibited the binding to the PRE. The coexpression of TFE3 in COS-7 cells transfected with the NPT2 gene promoter markedly stimulated the transcriptional activity. The feeding of a low P-i diet significantly increased the amount of TFE3 mRNA in the kidney. These findings suggest that TFE3 may participate in the transcriptional regulation of the NPT2 gene by dietary P-i.
• Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D-3 - Identification of a vitamin D-responsive element in the human NAPI-3 gene

  Y Taketani; H Segawa; M Chikamori; K Morita; K Tanaka; S Kido; H Yamamoto; Y Iemori; S Tatsumi; N Tsugawa; T Okano; T Kobayashi; K Miyamoto; E Takeda

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 273 (23) 14575 - 14581 0021-9258 1998/06 [Refereed]
   

  Vitamin D is an important regulator of phosphate homeostasis. The effects of vitamin D on the expression of renal Na+-dependent inorganic phosphate (P-i) transporters (types I and II) were investigated. In vitamin D-deficient rats, the amounts of type II Na+-dependent P-i transporter (NaPi-2) protein and mRNA were decreased in the juxtamedullary kidney cortex, but not in the superficial cortex, compared with control rats. The administration of 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) to vitamin D-deficient rats increased the initial rate of P-i uptake as well as the amounts of NaPi-2 mRNA and protein in the juxtamedullary cortex. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of the human type II Na+-dependent P-i transporter NaPi-3 gene was increased markedly by 1,25-(OH)(2)D-3 in COS-7 cells expressing the human vitamin D receptor. A deletion and mutation analysis of the NaPi-3 gene promoter identified the vitamin D-responsive element as the sequence 5'-GGGGCAGCAAGGGCA-3' nucleotides -1977 to -1963 relative to the transcription start site. This element bound a heterodimer of the vitamin D receptor and retinoid X receptor, and it enhanced the basal transcriptional activity of the promoter of the herpes simplex virus thymidine kinase gene in an orientation-independent manner. Thus, one mechanism by which vitamin D regulates P-i homeostasis is through the modulation of the expression of type II Na+-dependent P-i transporter genes in the juxtamedullary kidney cortex.
• Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D-3 - Identification of a vitamin D-responsive element in the human NAPI-3 gene

  Y Taketani; H Segawa; M Chikamori; K Morita; K Tanaka; S Kido; H Yamamoto; Y Iemori; S Tatsumi; N Tsugawa; T Okano; T Kobayashi; K Miyamoto; E Takeda

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 273 (23) 14575 - 14581 0021-9258 1998/06 [Refereed]
   

  Vitamin D is an important regulator of phosphate homeostasis. The effects of vitamin D on the expression of renal Na+-dependent inorganic phosphate (P-i) transporters (types I and II) were investigated. In vitamin D-deficient rats, the amounts of type II Na+-dependent P-i transporter (NaPi-2) protein and mRNA were decreased in the juxtamedullary kidney cortex, but not in the superficial cortex, compared with control rats. The administration of 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) to vitamin D-deficient rats increased the initial rate of P-i uptake as well as the amounts of NaPi-2 mRNA and protein in the juxtamedullary cortex. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of the human type II Na+-dependent P-i transporter NaPi-3 gene was increased markedly by 1,25-(OH)(2)D-3 in COS-7 cells expressing the human vitamin D receptor. A deletion and mutation analysis of the NaPi-3 gene promoter identified the vitamin D-responsive element as the sequence 5'-GGGGCAGCAAGGGCA-3' nucleotides -1977 to -1963 relative to the transcription start site. This element bound a heterodimer of the vitamin D receptor and retinoid X receptor, and it enhanced the basal transcriptional activity of the promoter of the herpes simplex virus thymidine kinase gene in an orientation-independent manner. Thus, one mechanism by which vitamin D regulates P-i homeostasis is through the modulation of the expression of type II Na+-dependent P-i transporter genes in the juxtamedullary kidney cortex.

Books etc

• 栄養科学シリーズNEXT 臨床栄養学実習第3版

  (Joint editor)講談社 2023/02 9784065301920
• Cadmium Toxicity-New Aspects in Human Disease, Rice Contamination, and Cytotoxicity

  Shinsuke Kido (Joint workDisturbance in Phosphorus Metabolism by Cadmium Exposure (Pages 179-190))Springer 2019/02 9789811336294
• 臨床栄養学実習第2版（栄養科学シリーズNEXT)

  塚原丘美; 共著; ネフローゼ症候群患者 (3.12 ネフローゼ症候群患者の栄養管理）、P124-1284-128)講談社サイエンティフィク 2017/03
• 新・臨床栄養学（栄養科学シリーズNEXTシリーズ）

  竹谷豊; 塚原丘美; 桑波田雅士; 坂上浩; 編 (Joint work13.1骨粗鬆症)講談社サイエンティフィク 2016/01
• ミネラルと摂取と老化制御－リン研究の最前線－

  宮本賢一; 新井英一; 下村吉治責任編集 (Contributor第2編リンと栄養、第6章 リン添加物 (P.69-P.87))建帛社 2014/05
• 臨床栄養、vol.124、No.3

  大西律子; 木戸慎介; 宮本賢一 (Joint work慢性腎臓病におけるリン管理、リン添加物の話題 （P.317-324))2014
• CLINICAL CALCIUM、vol.23 No.9

  木戸 慎介 (Joint workカドミウムや鉄などの重金属と骨代謝 （P.59-66))医薬ジャーナル社 2013
• CLINICA CALCIUM、vol.22 No.10

  木戸慎介; 野村憲吾; 佐々木祥平; 塩﨑雄治; 瀬川博子; 辰巳佐和子 (Joint workリン添加物に関する情報と栄養指導 （P.127-135))医薬ジャーナル社 2012
• CLINICAL CALCIUM、vol.22 No.10

  辰巳佐和子; 野村憲吾; 宮川敦美; 木戸慎介; 瀬川博子 (Joint workリンセンシングと腸管 （P.81-85))医薬ジャーナル社 2012
• CLINICAL CALCIUM、vol.22 No.10

  瀬川博子; 佐々木祥平; 向井朋; 真鍋舞; 木戸慎介; 辰巳佐和子; 宮本賢一 (Joint workリンの体内動態（腸管、腎臓における吸収と排泄機序／リン輸送体の機能作用）P.13-20)医薬ジャーナル社 2012
• 腎と骨代謝 Vol.25 No.1

  木戸慎介; 桑原頌治; 野村憲吾; 大井彰子; 辰巳佐和子; 瀬川博子; 宮本賢一 (Joint workFGF23の作用と作用機序 (P.25-31))日本メディカルセンター 2012
• Mechanosensing Biology

  Toshio Matsumoto; Rika Kuriwaka-Kido; Shinsuke Kido (Joint workMechanosensing and Signaling Crosstalk (157-166))Springer 2011
• 循環器医のための知っておくべき電解質異常

  大井彰子; 桑原頌治; 木戸慎介; 宮本賢一 (Joint work②リン，亜鉛，銅 (P.47-51))メディカルビュー社 2011
• 腎と透析，Aug.2010 8 Vol.69No.2

  宮本賢一; 山口誠一; 辰巳佐和子; 木戸慎介; 瀬川博子 (Joint workフォスファトニンとリン (P.200-202))東京医学社 2010
• 腎と骨代謝 vol.23 No.2

  辰巳佐和子; 菊井聡子; 花房悦世; 木戸慎介; 宮本賢一 (Joint workリン代謝と腸管)日本メディカルセンター 2010
• 臨床透析vol.26 no.1

  宮本賢一; 金子一郎; 古谷順也; 木戸慎介 (Joint workカルシウム／リン代謝調節機序の最近の進歩 （P.9-16))日本メディカルセンター 2010
• Nephrology FrontierVol.8 No.4 12月号

  宮本賢一; 辰巳佐和子; 金子一郎; 木戸慎介; 瀬川博子 (リン低下薬の今後の行方 （P.33-38))2009
• CKD-MBDハンドブック

  木戸慎介; 辰巳佐和子; 宮本賢一 (Joint workリンバランスとその調節機構 (P.25-30))日本メディカルセンター 2009
• カルシウム代謝概論

  木戸 慎介; 松本 俊夫 (Joint work内分泌・糖尿病科(特別増刊号、カルシウム・骨代謝の全て), 23 Suppl.3)科学評論社 2006
• 腎と骨代謝 18(1)

  木戸慎介; 井上大輔 (Joint work力学的負荷による骨芽細胞の分化誘導因子の転写制御 (P.31-38))日本メディカルセンター 2005
• 日本臨床 骨粗鬆症学―基礎・臨床研究の新しいパラダイム -62 Suppl 2

  木戸慎介; 井上大輔 (Joint workII.骨代謝調節系、破骨細胞の機能・骨吸収メカニズム、骨吸収促進因子 fosB/IL-11)日本臨床社 2004
• ホルモンと臨床 52 Suppl

  木戸慎介; 井上大輔; 松本俊夫 (Joint workGlucocorticoid Action in Osteoblasts.―ステロイドホルモン研究の進歩2003)医学の世界社 2003
• CLINICAL CALCIUM vol.13(1)

  木戸慎介; 井上大輔 (Joint work特集：PTHの新たな展開―骨粗鬆症における意義―Review PTHによる骨形成促進作用の発現機序 （P.14-18))医薬ジャーナル社 2003
• オステオアゴラ（中国・四国）秋季19

  木戸慎介; 井上大輔 (Joint workメカニカルストレスと細胞内情報伝達機構)2002
• 整形・災害外科

  木戸慎介; 井上大輔 (Joint work力学的負荷とfos family遺伝子 (P.1350-1351))2001
• 続発性骨粗鬆症マニュアル

  木戸慎介; 井上大輔 (Joint work栄養・食餌性因子 (P.126-P.132))ライフサイエンス出版 2000
• 栄養生化学 人体の構造と機能（栄養科学シリーズNEXTシリーズ）

  加藤秀夫; 中坊幸弘; 宮本賢一 (Joint work)

Conference Activities & Talks

• Verification of the Effectiveness of Black Soybean Seed Coat Extract in Maintaining Vascular Flexibility  [Not invited]

  木戸慎介; 川本萌; 小倉明奈; 森立夏; 安西正弘; 村瀬浩; 財満信宏; 森山達哉

  第78回日本栄養・食糧学会大会
• 医食農連携を基盤としたwithコロナの地域戦略 ～地域支援型農業（CSA)を導入した「医」と「農」を支える多様な連携軸の構築～  [Invited]

  木戸慎介

  2023年度公益社団法人滋賀県栄養士会研究教育事業部総会  2024/02
• 大学生と「官・産・学」で健康教育を目指す食育イベントについて  [Not invited]

  藤本美香; 山下和子; 村上華子; 渡辺紗弥佳; 藤原克美; 木戸慎介; 冨田圭子; 多賀敦; 安井梨紗; 村田積美; 市川勝義; 東田有智

  第27回日本病態栄養学会学年次学術集会  2024/01
• 家庭用調理ケア家電の調理特性について  [Not invited]

  水本千夏; 神岡実祐; 青柳美咲; 房晴美; 水野時枝; 向奥裕基; 北村光; 木戸慎介

  第22回日本栄養改善学会近畿支部会学術総会  2023/12
• フレイルチェック表による健康教室の効果について  [Not invited]

  清水満里子; 木戸慎介

  第21回日本栄養改善学会近畿支部学術総会  2023/03
• シンポジウム「教育と臨床を繫ぐ」 管理栄養士養成課程における「褥瘡」の学びについて～現状と課題～  [Invited]

  木戸慎介

  第19回日本褥瘡学会近畿地方会学術総会  2022/03
• たんぱく質の量・質的違いが食後の血糖変動に及ぼす影響の検討  [Not invited]

  木戸慎介; 丸川藍里; 吉良夏帆; 濱田芳恵

  第19回日本栄養改善学会近畿支部会学術総会  2021/03
• １． タンパク質の量・質の違いが食後の血糖変動に及ぼす影響の検討  [Not invited]

  前塚美織; 田中美和; 木戸慎介

  第１８回日本栄養改善学会近畿支部学術総会  2020/03
• ２． 動物性食品に含まれるタンパク質並びにリンの低減化に有効な調理方法の開発  [Not invited]

  上西梢; 木戸慎介

  第１８回日本栄養改善学会近畿支部学術総会  2020/03
• 動物性食品に含まれるリンの低減化に有効な調理法の開発  [Not invited]

  上西梢; 安岡美総、冨田圭子、木戸慎介

  第66回日本栄養改善学会学術総会  2019/09
• 農学部生を対象とした健康診断を利用した生活習慣病一次予防対策  [Not invited]

  木戸慎介; 日下部友香; 荒井玲夢; 堀田百合香; 山崎優貴; 寺本陽美; 後藤房子

  第17回日本栄養改善学会近畿支部会抄録  2019/03 

  【背景】健康は栄養・運動・休養の3つのバランスを高いレベルで維持し続けることが必要であるが、大学生は進学などに伴う生活環境の変化によって体調を崩すことが少なくない。近畿大学農学部に在籍する学生の多くは健常であると考えられるが、BMIが基準を大きく外れるなど、健康を維持する上で看過できない潜在的リスクを抱える学生が一部見受けられる。【目的】生活習慣病一次予防に向けた栄養学的介入をおこなうことで、農学部生の健康維持・増進を目指すことを目的に、以下の検討を試みた。【方法】農学部学生支援課（医務室）との連携により4月検診結果を基にBMIを算出した。基準を大きく外れた学生を対象 (BMI≧30)に、栄養学的介入をおこなった。【結果】栄養学的介入を実施した対象者9名の殆どで体重減少を認め、また介入前後で食習慣の改善が見受けられた例もあった。一方で、食事記録並びに食物摂取頻度調査（FFQg）の結果から、対象者の多くに食事変容バイアスが見られるなど、過少申告は特に肥満者で著しい事が改めて示された。【考察】肥満は生活習慣病のリスクとなるため、一部の学生においては将来を見据え生活習慣を整える必要がある。また栄養学的介入は生活習慣病一次予防に向けた支援として有効であった。しかし食物摂取頻度調査においては分量に関する知識や感覚の違いおよび過少申告による誤差の可能性が考えられた。今後我々はBMIが基準を大きく外れている学生に対し、集団的な介入および食への関心や知識を高めるような環境作りを行う必要がある。
• 慢性腎臓病患者の新たな食事・栄養療法の開発 ～リン供給源の違いがCKD患者のリン代謝動態に及ぼす影響について～  [Not invited]

  木戸慎介; 上西梢; 安岡美総; 冨田圭子; 加藤博一

  第65回日本栄養改善学会学術総会  2018/09 

  【背景】腎機能が低下した慢性腎臓病（CKD）患者では食事からの過剰なリンを尿として排泄できず、高リン血症を招く恐れがある。高リン血症は心血管疾患などの致命的な合併症を引き起こす可能性があることから、CKD患者にとってリンの制限は重要である。しかし、食品中のリンの多くはタンパク質と結合しているためリンのみを制限することは困難である。一方で過度のタンパク質の制限は患者の栄養状態の悪化を招くことから、適切なタンパク質量を確保し、尚且つリンを選択的に制限することが求められる。我々は昨年度の本大会において、健常者を対象に食事中のリン供給源（タンパク質）を植物性食品中心とすることで、リンを選択的に制限できることを明らかにしている。そこで本研究では、健常者において得られた成績がCKD患者においても有効であるか否かについて、臨床研究を試みた。【方法】対象はA医院に通院のCKDステージ3bの70代男性3名とした。動物性タンパク質比率70%（動物70%食）あるいは植物性タンパク質比率70%（植物70%食）に調整した試験食(慢性腎臓病に対する食事療法基準2014年版に準拠し、双方共に３大栄養素、リン、カルシウム、食塩量は等量)の2種類の食事を提供した際の体内リン代謝動態を比較した。実験は、クロスオーバー試験とし、1か月の休息期間後、同様の試験を行った。【結果】食後の尿中リン排泄は、動物70%食群と植物70%食群で差は認められなかった。一方で血中リン濃度において、動物70％食群に比べ植物70％食群で食後血中リン濃度の上昇が穏やかであった。【考察】本成績は、健常者と同様に、CKD患者においても植物性タンパク質中心の食事をとることで、極端にたんぱく質を制限することなく、効率の良いリン管理が可能であることを示唆するものであり、CKD患者の病態改善の一助となることが期待される。
• たんぱく質源の異なる食事における調理前後のリンおよびカリウム含量の比較検討～CKD患者への応用を目指して～  [Not invited]

  上西梢; 安岡美総; 冨田圭子; 加藤博一; 木戸慎介

  第65回日本栄養改善学会学術総会  2018/09 

  【背景】健常な人の場合、体内のリン並びにカリウムの濃度は、腎臓による排泄と再吸収の機能によって一定に保たれている。しかしながら、腎機能が低下した慢性腎臓病（CKD）患者では、体内にリンやカリウムが蓄積し、副甲状腺機能亢進症や異所性石灰化の原因となる高リン血症や、不整脈や心停止の原因となる高カリウム血症を招く恐れがある。現在CKDの食事療法では病期に合わせてリンやカリウムの制限がおこなわれているが、調理過程で損失の多いカリウムに対して、リンの多くはタンパク質と共存することから食事管理が困難である。一方で我々はこれまでに、同量のリン含量であっても植物性タンパク質の多い食事を摂取することで、動物性タンパク質の多い食事に比べ、食後の血中リン濃度の上昇を穏やかにすることを明らかにしている。しかしながら、植物性タンパク質の多い食事にはカリウムが多く含まれる問題点がある。但し、先行研究では食事の栄養価は食材の生の成分値で算出したため調理による損失を考慮していない。そこで本研究では、タンパク質源の異なる食事におけるリン、カリウムの調理損失に着目し、植物性タンパク質の多い食事と動物性タンパク質の多い食事に含まれるリン並びにカリウム含量を調理前後で比較検討した。【方法】試料は先行研究において健常者に試験食として提供した、動物性タンパク質が多い食事（動物食）と植物性タンパク質が多い食事（植物食）を用いた（双方共に３大栄養素、リン、カルシウム、食 塩量は等量）。試料は、調理前と調理後にミキサーにかけ均一にしたものを用い、リン、カリウム含量を測定し損失率を算出した。【結果】植物食では調理前に比べ調理後でリンは3％、カリウムは53％の損失を示した。一方、動物食では調理前後でリンは5％、カリウムは11％の損失を示した。【考察】本成績は、植物性タンパク質を多く含む食事がリンのみならずカリウム制限も実施できる可能性を示唆するものであり、CKD患者に向けた食事療法として活用できるものと期待される。
• CKD患者の病態進展阻止に有効な新たな食事・栄養療法の開発  [Not invited]

  木戸慎介; 上西梢; 山本麻伊; 吉田衣里; 安岡美総; 冨田圭子; 加藤博一

  第37回食事療法学会  2018/03 

  【背景】CKDに伴う骨ミネラル代謝異常 (CKD-MBD)の概念が提唱されて以来、血清リン（P）濃度と生命予後との関連性が注目されている。P排泄不全を呈するCKD患者において食事性P管理は極めて重要であるが、Pは多くの食品に含まれていること、その多くはたんぱく質と共存することなどから、その実践は容易ではない。そこで本研究では、食事性P管理の新たな方策として、Pの体内利用率が食材により異なる点に着目し、食事に含まれるたんぱく質の違いが体内P代謝動態に及ぼす影響について検討した。【方法・結果】対象者は当学科所属の20代健常男子学生とした。動物性たんぱく質比率70％(動70%食)あるいは植物性たんぱく質比率70％（植70％食）に調整した試験食（双方共にカロリー、三大栄養素、P量を同等となるよう調整）を喫食後の体内リン代謝動態を検討した。その結果、食後の尿中P排泄は動70％食群で顕著な増加がみられたが、植70％食群では軽微であった。なお双方の血中P濃度に大きな変動は認められなかった。植70％食は食物繊維を多く含む事から、尿中P排泄の低下の一因として食物繊維の関与が考えられる。そこで次に動70％食・植70％食に加えて、植70％食と同等になるよう食物繊維の量を調整した動70％食（動70％DF食）の3種を喫食した際の体内P代謝動態を比較した。その結果、動70％食群でみられた食後尿中P排泄の増加は、食物繊維量を植70％食群と同等に調整すること（動70％DF食）で改善された。【考察】CKD患者に対するたんぱく制限の有効性については未だ議論の分かれるところであり、その要因の1つとして過度のたんぱく制限による栄養状態の悪化が懸念されている。本成績は過度のたんぱく制限を伴わずにP制限を実施できる新たな可能性を示すものであり、CKD患者の病態進展阻止の一助となることが期待される。
• 慢性腎臓病患者の新たな食事・栄養療法の開発  [Not invited]

  上西梢; 木戸慎介

  第64回日本栄養改善学会学術集会  2017/09
• 慢性腎臓病患者の新たな食事・栄養療法の開発～食物繊維が体内リン代謝動態に及ぼす影響～  [Not invited]

  上西梢; 安岡美総; 冨田圭子; 加藤博一; 木戸慎介

  第64回日本栄養改善学会学術集会  2017/09
• 未利用資源である大和橘の有効活用～果皮抽出物が有する抗メタボ効果の検証～  [Not invited]

  上西梢; 池田望; 中山晴江; 富研一; 林孝洋; 木戸慎介

  第71回日本栄養・食糧学会大会  2017/05
• 慢性腎臓病患者の新たな食事・栄養療法の開発～リン管理における 植物性たんぱく質の有効性について～  [Not invited]

  上西梢; 川端佑季; 野方美里; 木戸慎介

  第15回日本栄養改善学会近畿支部学術総会  2016/12 

  【背景】慢性腎臓病（CKD）患者でみられる高リン血症は、心血管イベントなどの致命的な合併症を引き起こすことから、当該患者における食事性リン管理は必須である。血中リン濃度は、食事中のリン含量に左右されるが、リンはタンパク質と結合していることから、リンのみを制限することは容易ではない。そこで本研究では、選択的にリンを制限する新たな手法として、リンの生体内利用率が食材により異なる点に着目し、食事中のリン供給源の違いが体内リン代謝動態に及ぼす影響について検証を試みた。【方法】対象者は当学科に所属の20代の健常学生とした。なお本研究は本学生命倫理員会の承認を得た上で実施した。（実験Ⅰ）動物性由来リン比率70%あるいは植物性由来リン比率70%に調整した試験食(双方共にタンパク質、リン量は等量)を対象者に昼食として供した際の体内リン代謝動態を比較した。（実験Ⅱ）実験Ⅰと同様の栄養価の食事を5日間継続的に被験者に提供し、体内リン代謝動態への影響を検討した。【結果】（実験Ⅰ）の植物性リン70%食群では、動物性リン70%食群に比して試験食摂取後の血中リン濃度並びに尿中リン濃度の上昇が緩やかであった。（実験Ⅱ）の植物性リン70％食群では、動物性リン70％食群と比べて血中リン濃度に差は認められなかったが、尿中リン濃度は、5日間継続的に低い値を維持した。【考察】植物性由来のリンを多く含む食事では食後の血中リン濃度の上昇が穏やかであることが明らかとなった。本成績は、早期リン制限による腎機能悪化進展阻止に向けた新たな食事・栄養療法として、CKD患者の病態改善の一助となる可能性が示唆された。
• 慢性腎臓病患者向け食事療法が抱える栄養学的課題の抽出：ビッグデータを活用した新たな栄養学的アプローチ  [Not invited]

  木戸慎介; 冨田史子; 上西梢; 小島誠也; 加藤博一; 安岡美総; 冨田圭子

  第15回日本栄養改善学会近畿支部学術総会  2016/12 

  【背景】慢性腎臓病（CKD）における食事療法ではたんぱく質制限を中心とする厳しい制限により微量栄養素等の欠乏を招く恐れがあるが、その詳細は未だ不明な点が多く残されている。そこで本研究では、既存のCKD患者向け献立を網羅解析することで、その問題点並びに解決策を模索した。【方法】本検討では、腎臓病食品交換表に準拠したCKD患者向け献立を収載する市販書籍を解析対象とした。当該書籍に収載の献立（朝昼夕毎に51食、計153食）をデジタルデータ化し、得られた全ての1日分の組み合わせ（513＝約13万通り）のうち、CKD食事療法基準（2014年版）ステージ3bを満たす組み合わせ約9万通りを抽出し、これらの献立に含まれる栄養素の過不足について検証した。【結果】抽出したCKD食1日分（9万通り）に含まれる各種栄養成分について、「日本人の食事摂取基準2015年版」を基に充足率を求めたところ、ビタミンではVit.B群やVit.Dで、またミネラルではCa、Mg、Znなど、多数の微量栄養素の不足を確認した。【考察】CaやVit.Dの不足はCKDに伴う骨ミネラル代謝障害のリスクであることから、これらの栄養素に配慮した献立作成の必要性が改めて浮き彫りとなった。またこうした微量栄養素の不足は対象群である常食では認められなかったことから、たんぱく質制限を中心とした腎臓病食特有の問題であることが推測される。一方で、Znのように不足しがちであるものの、必ずしもたんぱく質制限との間に強い相関を認めない栄養素も存在したことから、食材の組み合わせによっては、CKD食においても食事摂取基準を十分満たすことが可能であると考えられる。しかしながら、多数の栄養成分を適切に管理しつつ、「単位」のような指標を用いて献立を作成することは困難である。このため、我々の作成したデータベースをはじめとした情報技術を用いることにより、多数の栄養成分に配慮した食事管理法は、今後益々必要とされるものと考えられる。
• 情報技術を基盤とした網羅解析による慢性腎臓病患者向け食事療法に潜在する栄養学的課題の抽出  [Not invited]

  木戸慎介; 上西梢; 加藤博一; 安岡美総; 冨田圭子

  第63回日本栄養改善学会学術総会  2016/09
• 慢性腎臓病患者の新たな食事・栄養療法の開発～タンパク質源の違いが体内リン代謝動態に及ぼす影響～  [Not invited]

  上西梢; 安岡美総; 冨田圭子; 加藤博一; 木戸慎介

  第63回日本栄養改善学会学術総会  2016/09
• 情報技術を基盤とした網羅解析による慢性腎臓病患者向け食事療法に潜在する栄養学的課題の抽出  [Not invited]

  木戸慎介; 上西梢; 安岡美総; 冨田圭子

  奈良県栄養士会平成28年度研究発表会  2016/08
• Examination of a cultivation system with polyester fiber media and quantitative nutrient manage  [Not invited]

  Shinsuke Kido

  The Japanese Society for Horticultural Science  2016/03
• 在宅食事療法の栄養素情報の分析と動的な献立計画支援手法の提案  [Not invited]

  小島誠也; 冨田圭子; 木戸慎介; 森田晶; 金谷重彦; 稲村真弥; 上西梢; 高富貴史; 山本豪志朗; サンドアクリスチャン; 加藤博一

  電子情報通信学会－食メディア研究会  2016/03
• 慢性腎臓病の発症・進展に関わるリン利尿因子FGF23の動態と治療への展開  [Not invited]

  梶原千裕; 松林英里; 上西梢; 木戸慎介

  第14回日本栄養改善学会近畿支部学術総会  2015/12
• 慢性腎臓病の発症・進展におけるリン利尿因子FGF23の関与とその進展予防に向けた新たな食事療法の開発  [Not invited]

  木戸慎介; 上西梢

  第62回日本栄養改善学会  2015/09
• 高血圧に併存する骨代謝障害の病態解析－脳卒中易発症性高血圧自然発症ラットを用いて－  [Not invited]

  上西梢; 東千尋; 内田彩華; 木戸慎介

  第18回日本病態栄養学科年次学術集会  2015/01
• FGF23を介した腎臓－骨のリン恒常性維持機構に対するカドミウムの攪乱作用  [Not invited]

  木戸慎介; 瀬川博子; 辰巳佐和子; 宮本賢一

  第41回日本毒性学会学術年会  2014/07
• The elucidation of molecular pathogenesis involved in the onset and progression of lifestyle disease which are associated with high-blood pressure.  [Not invited]

  Shinsuke Kido

  第６８回日本栄養・食糧学会大会  2014/05
• 胎児期の低栄養曝露による生活習慣病の増悪化とその予防－脳卒中易発症性高血圧症自然発症ラットを用いて－  [Not invited]

  上西梢; 竹森久美子; 木戸慎介; 米谷俊; 村上哲男

  第17回日本病態栄養学会学術集会  2014/01
• 慢性腎臓病に併存する骨ミネラル代謝障害（CKD-MBD）の発症並びに進展におけるFGF23の関与  [Not invited]

  木戸慎介; 越智美佐子; 藤原真理奈; 向井朋; 塩﨑雄治; 瀬川博子; 辰巳佐和子; 宮本賢一

  第67回日本栄養・食糧学会大会  2013/05
• 慢性腎臓病におけるFGF23産生亢進の分子機能解析  [Not invited]

  木戸慎介; 越智美佐子; 藤原真理奈; 向井朋; 瀬川博子; 辰巳佐和子; 宮本賢一

  第16回日本病態栄養学会年次学術集会  2013/01
• Expression of type II Na-dependent phosphate cotransporter Npt2c and vacuole formation in proximal tubule epithelial cells  [Not invited]

  塩崎雄治; 大西沙織; 大井彰子; 杉野紗貴子; 蓑島さくら; 瀬川博子; 辰巳佐和子; 宮本賢一; 木戸 慎介; 伊藤美紀子

  第86回日本生化学会大会  2013  パシフィコ横浜（神奈川県）  第86回日本生化学会大会
   

  Na依存性無機リン酸輸送担体Npt2cは高カルシウム尿を伴う遺伝性低リ ン血性クル病（HHRH）の原因遺伝子であることが報告されている。しかしながら、Np t2c欠損マウスでは、ヒトで観察されるような低リン血症やクル病様所見を示さない ため、未だにその役割は不明である。一方、Npt2aは腎近位尿細管上皮細胞に発現し 、リン再吸収の律速段階を担う。げっ歯類においては、Npt2aがリン再吸収の70%を担 うのに対し、Npt2cは補助的な役割を担っている。Npt2cの生理学的な役割を解明する ためには、Npt2cを内因性に発現している細胞を用いる必要がある。OK細胞（フクロ ネズミ由来腎近位尿細管細胞）は、培養日数を経て分化し微絨毛が発達し、Npt2aの 発現が誘導される。本研究において、OK細胞に発現するNpt2cを同定し、特異抗体を 作製して、培養後の変化を調べた。内因性Npt2c発現は、OK細胞の未分化時に高く、 分化後では著しく発現が低下した。未分化細胞においてNpt2c
• Molecular mechanism of cadmium (Cd) dependent fibroblast growth factor 23 secretion in bone  [Not invited]

  Kido S; Fujihara M; Nomura K; Sasaki S; Shiozaki Y; Segawa H; Tatsumi S; Miyamoto K

  American Society of Nephrology for Kidney Week 2012, San Diego, CA  2012/10
• カドミウム汚染によるリン代謝異常・骨軟化症発症機序の検討  [Not invited]

  木戸慎介; 藤原真理奈; 瀬川博子; 辰巳佐和子; 宮本賢一

  第30回日本骨代謝学会  2012/07
• Muscle atrophy in patients with CKD results from FGF23/Klotho-mediated suppression of Insulin/IGF-I signaling  [Not invited]

  Kido S; Hashimoto Y; Segawa H; Tatsumi S; Miyamoto KI

  XVI International Congress on Nutrition and Metabolism in Renal Disease 2012, Honolulu, Hawaii  2012/06
• 慢性腎臓病患者におけるFGF23産生亢進の分子機能解析  [Not invited]

  木戸慎介; 藤原真理奈; 向井朋; 瀬川博子; 辰巳佐和子; 宮本賢一

  第66回日本栄養・食糧学会大会  2012/05
• カドミウム汚染によるリン代謝異常：骨軟化症発症機序の検討  [Not invited]

  藤原真理奈; 木戸慎介; 瀬川博子; 辰巳佐和子; 宮本賢一

  第15回日本病態栄養学会学術集会  2012/01
• 糖尿病に併存する腎傷害・骨障害の発症及び進展におけるFGF23の関与  [Not invited]

  木戸慎介; 橋本由衣; 藤原真理奈; 遠藤逸朗; 瀬川博子; 辰巳佐和子; 松本俊夫; 宮本賢一

  第15回日本病態栄養学会学術集会  2012/01
• 糖尿病合併症発症におけるFGF23/Klothoの関与  [Not invited]

  橋本由衣; 木戸慎介; 藤原真理奈; 近藤剛史; 瀬川博子; 遠藤逸朗; 辰巳佐和子; 松本俊夫; 宮本賢一

  第４４回日本栄養食糧学会中四国支部大会  2011/11
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与  [Not invited]

  木戸慎介; 藤原真理奈; 中川航司; 瀬川博子; 辰巳佐和子; 宮本賢一

  第２９回日本骨代謝学会学術集会  2011/07
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与  [Not invited]

  木戸慎介; 藤原真理奈; 中川航司; 瀬川博子; 辰巳佐和子; 宮本賢一

  第65回日本栄養・食糧学会大会  2011/05
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与  [Not invited]

  木戸慎介; 藤原真理奈; 中川航司; 瀬川博子; 辰巳佐和子; 宮本賢一

  第14回日本病態栄養学会年次学術集会  2011/01
• FGF23/Klothoを介した新たな腎尿細管リン・カルシウム代謝調節機構の解明  [Not invited]

  坂田雅映; 木戸慎介; 橋本由衣; 辰巳佐和子; 瀬川博子; 松本俊夫; 宮本賢一

  第14回日本病態栄養学会年次学術集会  2011/01
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与  [Not invited]

  藤原真里奈; 木戸慎介; 坂田雅映; 荒波史; 瀬川博子; 辰巳佐和子; 宮本賢一

  第43回日本栄養/食糧学会中国四国支部大会  2010/11
• イタイイタイ病に見られるCd骨症（骨軟化症）の発症・進展におけるFGF23の関与  [Not invited]

  木戸慎介; 中川航司; 橋本由衣; 坂田雅映; 辰巳佐和子; 荒波史; 瀬川博子; 宮本賢一

  第28回日本骨代謝学会  2010/07
• 糖 尿病発症における抗老化因子Klothoの関与  [Not invited]

  橋本由衣; 木戸慎介; 中川航司; 坂田雅映; 佐々木祥平; 辰巳佐和子; 宮本賢一

  第64回日本栄養・食糧学会大会  2010/03
• 糖尿病性骨症の発症機序の解明：終末糖化産物 (AGEs)による Canonical Wnt経路抑制機序の解析  [Not invited]

  中川航司; 木戸慎介; 遠藤逸朗; 坂田雅映; 橋本由衣; 佐々木祥平; 辰巳佐和子; 松本 俊夫; 宮本賢一

  第64回日本栄養・食糧学会大会  2010/03
• シナカルセト塩酸塩によるリン管理  [Not invited]

  菊井聡子; 辰巳佐和子; 野村憲吾; 斎藤友紀子; 塩崎雄治; 山口誠一; 木戸慎介; 宮本 賢一

  第13回日本病態栄養学会年次学術集会  2010/01
• 糖尿病性骨症の発症機序の解析：ユビキチン化分解経路に及ぼすメイラード反応後期生成物 (AGEs)の影響  [Not invited]

  木戸慎介; 中川航司; 遠藤逸郞; 坂田雅映; 蒲原彰宏; 橋本由衣; 佐々木祥平; 辰巳佐和子; 松本俊夫; 宮本賢一

  第13回日本病態栄養学会年次学術集会  2010/01
• 寿命調節因子Klothoによるリン代謝調節調節  [Not invited]

  大井 彰子; 西山 俊; 伊藤 美紀子; 杉野 紗貴子; 木戸 慎介; 辰巳 佐和子; 瀬川 博子; 宮本 賢一

  第13回日本病態栄養学会年次学術集会  2010/01
• 糖尿病性骨症の発症機序の解析：ユビキチン化分解経路に及ぼすメイラード反応後期生成物（AGEs）の影響  [Not invited]

  中川航司; 木戸慎介; 遠藤逸朗; 坂田雅映; 蒲原彰宏; 橋本由衣; 佐々木祥平; 辰巳佐和子; 松本俊夫; 宮本賢一

  第42回日本栄養・食糧学会中国四国支部大会  2009/11
• CLCA6(Chloride channel calcium activated 6)のリン代謝への関与  [Not invited]

  斎藤友紀子; 辰巳佐和子; 野村憲吾; 菊井聡子; 山口誠一; 塩崎雄治; 木戸慎介; 金子一郎; 瀬川博子; 宮本賢一

  第42回日本栄養・食糧学会中国四国支部大会  2009/11
• Mechanical stress enhances osteoblast differentiation via canonical Wnt pathway  [Not invited]

  Kido S; Kuriwaka R; Endo I; Ito Y; Matsumoto T

  2nd joint meeting of the IBMS&ANZBMS, Sydney, Australia  2009/05
• 肝臓切除による低リン血症発症メカニズムの解明  [Not invited]

  野村憲吾; 辰巳佐和子; 八杉昌憲; 菊井聡子; 斎藤友紀子; 木戸慎介; 伊藤美紀子; 宮本賢一

  第63回日本栄養・食糧学会大会  2009/05
• 老化関連因子klothoによるリン代謝調節機構の解明  [Not invited]

  西山俊; 伊藤美紀子; 大井彰子; 杉野紗貴子; 坂田雅映; 蒲原彰宏; 木戸慎介; 辰巳佐和子; 瀬川博子; 宮本賢一

  第63回日本栄養・食糧学会大会、長崎  2009/05
• 2つのリン酸輸送体分子による生体内リン代謝調節機構の解明  [Not invited]

  伊藤美紀子; 蒲原彰宏; 大井彰子; 西山俊; 杉野沙貴子; 坂田雅映; 辰巳佐和子; 木戸慎介; 瀬川博子; 宮本賢一

  第63回日本栄養・食糧学会大会  2009/05
• 加齢に伴う骨形成低下のメカニズム：酸化ストレスの関与  [Not invited]

  木戸慎介; 栗若里佳; 遠藤逸朗; 伊藤祐司; 宮本賢一; 松本俊夫

  第63回日本栄養・食糧学会大会  2009/05
• 加齢に伴う骨形成低下の分子メカニズム：酸化ストレスの関与  [Not invited]

  木戸慎介; 栗若里佳; 宮本賢一; 松本俊夫

  第12回日本病態栄養学会年次学術集会  2009/01
• 力学的負荷はCanonical Wnt経路を介して骨芽細胞分化を促進する  [Not invited]

  木戸慎介; 栗若里佳; 松本俊夫

  第26回日本骨代謝学会  2008/10
• Coactivator MBF1 binds to JunD and protects its transcriptional activity against oxidative stress to prevent age-related suppression of osteoblast differentiation  [Not invited]

  Kido S; Kuriwaka R; Matsumoto T

  30th Annual Meeting of American Society for Bone and Mineral Research (ASBMR),Montreal, Canada  2008/09
• 力学的負荷による骨芽細胞分化の制御メカニズム ~Mechanical stress-induced signaling of osteoblast differentiation  [Invited]

  木戸 慎介

  第25回日本骨代謝学会  2008/07
• MBF1は酸化ストレスに抗して骨芽細胞分化を促進する  [Not invited]

  木戸慎介; 栗若里佳; 松本俊夫

  第24回日本骨代謝学会  2007/07
• BMP-2 enhances mechanical stress-induced osteoblastic differentiation of Smad1/delta-fosB/JunD complex on IL-11 gene promoter  [Not invited]

  Kido S; Kuriwaka R; Miyamoto T; Taniguchi H; Matsumoto T

  28th Annual Meeting of American Society for Bone and Mineral Research (ASBMR), Philadelphia, PA, USA.  2006/09
• 力学的負荷による骨芽細胞分化の誘導はBMP-2によりAP-1/Smad複合体を介して促進される  [Not invited]

  木戸慎介; 栗若里佳; 宮本貴子; 谷口寿章; 松本俊夫

  第23回日本骨代謝学会  2006/07
• グルココルチコイド過剰による骨形成低下の機序  [Not invited]

  木戸慎介; 伊藤祐司; 井上大輔; 松本俊夫

  第79回日本内分泌学会学術総会  2006/05
• 力学的負荷による骨形成促進シグナルに関わる転写因子群の機能解析  [Invited]

  木戸慎介; 井上大輔; 今村健志; 宮園浩平; 谷口寿章; 松本俊夫

  第２７回日本分子生物学会年会  2004/12
• A novel mechanical stress-induced signaling pathway leading to protein kinase C delta-dependent Smad1 activation in osteoblast  [Not invited]

  KIDO Shinsuke

  26th Annual Meeting for the American Society for Bone and Mineral Research (ASBMR), Seattle, USA  2004/10
• 力学的負荷はPKC依存性かつBMP受容体非依存性にSmad1を活性化して骨芽細胞分化を促進する  [Not invited]

  木戸慎介; 井上大輔; 今村健志; 宮園浩平; 山内英美子; 宮本貴子; 谷口寿章; 松本俊夫

  第２２回日本骨代謝学会  2004/08
• A novel mechanical stress-induced signaling pathway leading to Smad1/5/8 activation in osteoblasts  [Not invited]

  Kido S; Inoue D; Imamura T; Miyazono K; Matsumoto T

  25th Annual Meeting for the American Society for Bone and Mineral Research (ASBMR), Minneapolis  2003/09
• Interleukin-11 is an osteogenic cytokine that inhibits osteoblast apoptosis: upregulation of Bcl-2 and synergism with estrogen  [Not invited]

  Kido S; Inoue D; Kato S; Yoshida K; Matsumoto T

  1st Joint Meeting of IBMS/JSBMR, Okayama, Japan  2003/06
• Roles for interleukin-11 down-regulation in glucocorticoid suppression of bone formation  [Not invited]

  Kido S; Inoue D; Kato S; Ito Y; Matsumoto T

  11th ICHS&7th ICHC Joint Meeting (International Congress on Hormonal Steroids and Hormones and cancer), Fukuoka, Japan  2002/10
• Down-regulation of interleukin-11 may be involved in the pathogenesis of glucocorticoid-induced osteoporosis  [Not invited]

  Kido S; Inoue D; Kato S; Ito Y; MatsumotoT

  24th Annual Meeting for the American Society for Bone and Mineral Research (ASBMR), San Antonio, Texas , USA  2002/09
• 力学的負荷による骨形成促進機構におけるfosB/IL-11経路の活性化機序  [Not invited]

  木戸慎介; 井上大輔; 答島恵美子; 松本俊夫

  第２０回日本骨代謝学会  2002/07
• 加齢に伴う骨形成低下のメカニズム：AP-1/IL-11カスケードの役割  [Not invited]

  木戸慎介; 井上大輔; 加藤修司; 伊藤祐司; 松本俊夫

  第４４回日本老年医学会学術集会  2002/06
• Interleukin-11 is an osteogenic cytokine that inhibits osteoblast apoptosis  [Not invited]

  Kido S; Inoue D; Kato S; Ito Y; Matsumoto T

  9th Workshop on Cell Biology of Bone and Cartilage in Health and Disease, Davos, Switzerland  2002/03
• 骨形成促進シグナルにおけるAP-1/IL-11カスケードの活性化・作用機序とその病態生理学的役割  [Not invited]

  木戸慎介; 井上大輔; 松本俊夫

  第２４回日本分子生物学会年会  2001/12
• AP-1/interleukin-11 signaling cascades may be involved in PTH-induced bone formation: ERK-dependent induction of delta-fosB and IL-11 by hPTH  [Not invited]

  Kido S; Inoue D; Matsumoto T

  23th Annual Meeting for the American Society for Bone and Mineral Research (ASBMR), Phoenix, Arizona, USA  2001/10
• Activation of a Ca2+/ERK/Delta-fosB (AP-1) cascade by mechanical stress in osteoblasts, leading to up-regulation of an osteogenic cytokine, interleukin-11  [Not invited]

  Kido S; Inoue D; Tohjima E; Kato S; Matsumoto T

  23th Annual Meeting for the American Society for Bone and Mineral Research (ASBMR), Phoenix, Arizona, USA  2001/10
• 力学的負荷による骨形成促進機構におけるfosB/IL-11経路の活性化機序  [Not invited]

  木戸慎介; 井上大輔; 答島恵美子; 松本俊夫

  第１９回日本骨代謝学会  2001/07
• 副甲状腺ホルモン (PTH)によるAP-1/IL-11カスケードの活性化とその機序  [Not invited]

  木戸慎介; 井上大輔; 松本俊夫

  第７４回日本内分泌学会学術総会  2001/06
• Potential roles for AP-1/Interleukin-11 pathways in mechanical stress-induced bone formation  [Not invited]

  Kido S; Inoue D; Tohjima E; Matsumoto T

  International Bone and Mineral Society Forum （IBMF), Amsterdam, Netherland  2001/06
• 力学的負荷による骨形成促進機構におけるfos family遺伝子の役割  [Invited]

  木戸慎介; 井上大輔; 松本俊夫

  第２３回日本分子生物学会  2000/12
• Expression of RANK is dependent upon differentiation into macrophage/osteoclast lineage.  [Not invited]

  Kido S; Inoue D; Matsumoto T

  22th Annual Meeting for the American Society for Bone and Mineral Research （ASBMR),Toronto, Ontario, Canada  2000/09
• 力学的負荷による骨形成促進機構におけるfos family遺伝子の役割  [Not invited]

  木戸慎介; 井上大輔; 斉賀美恵子; 松本俊夫

  第１８回日本骨代謝学会  2000/07

MISC

• 古くて新しい課題 重金属研究の新展開 FGF23を介した腎臓 骨のリン恒常性維持機構に対するカドミウムの攪乱作用

  木戸 慎介; 瀬川 博子; 辰巳 佐和子; 宮本 賢一  The Journal of Toxicological Sciences  39-  (Suppl.)  S27  -S27  2014/07
• 骨細胞死滅マウスにおけるカルシウム/リン代謝異常機構について

  辰巳佐和子; 藤田みゆき; 藤井理; 野村憲吾; 木戸慎介; 瀬川博子; 宮本賢一  日本病態栄養学会誌  17-  (Supplement)  S.126  -126  2013/12
• 胎児期の低栄養暴露による生活習慣病の増悪化とその予防 脳卒中易発症性高血圧自然発症ラットを用いて

  上西 梢; 竹森 久美子; 木戸 慎介; 米谷 俊; 村上 哲男  日本病態栄養学会誌  17-  (Suppl.)  S  -200  2013/12
• 特集 続発性骨粗鬆症 ～骨脆弱性をもたらす病態概念の拡がり～ Topics カドミウムや鉄などの重金属と骨代謝

  木戸慎介  CLINICAL CALCIUM  23-  (9)  59  -66  2013/08
• 骨とリン利尿因子

  辰巳佐和子; 木戸慎介; 瀬川博子; 宮本賢一  日本透析医学会雑誌  46-  (Supplement 1)  358  2013/05
• 肝臓切除患者における低リン血症発症機構の解明

  野村憲吾; 辰巳佐和子; 宮川淳美; 岡奈都紀; 塩崎雄治; 木戸慎介; 瀬川博子; 佐野光枝; 福渡努; 柴田克己; 宮本賢一  日本栄養・食糧学会大会講演要旨集  67th-  173  -173  2013/04
• 慢性腎臓病に併存する骨ミネラル代謝障害(CKD‐MBD)の発症並びに進展におけるFGF23の関与

  木戸慎介; 越智美佐子; 藤原真理奈; 向井朋; 塩崎雄治; 瀬川博子; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  67th-  190  -190  2013/04
• Nampt^+/-のリン代謝の解析

  宮川淳美; 辰巳佐和子; 野村憲吾; 木戸慎介; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  67th-  172  2013/04
• リン利尿におけるKlothoの役割

  佐々木祥平; 瀬川博子; 大西沙織; 森絢加; 向井朋; 真鍋舞; 日下裕里; 木戸慎介; 辰巳佐和子; 宮本賢  日本腎臓学会誌  55-  (3)  366  -366  2013/04
• 近位尿細管上皮細胞におけるNa⁺依存性無機リン酸輸送担体Npt2cの発現調節とVacuole形

  塩崎雄治; 瀬川博子; 大西沙織; 大井彰子; 杉野紗貴子; 簑島さくら; 伊藤美紀子; 木戸慎介; 辰巳佐和子; 宮本賢一  日本生化学会大会(Web)  86th-  2T11P-09(2P-182) (WEB ONLY)  -09  2013
• 尿細管リン利尿におけるKlothoの役割

  佐々木祥平; 瀬川博子; 大西沙織; 森絢加; 向井朋; 真鍋舞; 日下裕里; 木戸慎介; 辰巳佐和子; 宮本賢一  日本生化学会大会(Web)  85th-  2T05-09 (WEB ONLY)  -09  2012/12
• 骨細胞死滅マウスのリン代謝異常について

  辰巳佐和子; 釜谷達哉; 野村憲吾; 藤田みゆき; 木戸慎介; 瀬川博子; 宮本賢一  季刊腎と骨代謝  25-  (4)  343  -344  2012/10
• 栄養とリン~新しい展開と課題~リン添加物に関する情報と栄養指導

  木戸慎介; 野村憲吾; 佐々木祥平; 塩崎雄治; 瀬川博子; 辰巳佐和子  Clinical Calcium  22-  (10)  1583  -1591  2012/09
• 栄養とリン~新しい展開と課題~リンの体内動態(腸管,腎臓における吸収と排泄機序/リン輸送体の機能作用)

  瀬川博子; 佐々木祥平; 向井朋; 真鍋舞; 木戸慎介; 辰巳佐和子; 宮本賢一  Clinical Calcium  22-  (10)  1469  -1476  2012/09
• 栄養とリン~新しい展開と課題~リンセンシングと腸管

  辰巳佐和子; 野村憲吾; 宮川淳美; 木戸慎介; 瀬川博子  Clinical Calcium  22-  (10)  1537  -1541  2012/09
• 【カドミウム研究の現状と今後の展望-疫学研究から分子機構まで】カドミウム曝露によるリン代謝異常 FGF23産生亢進機序の検討

  木戸 慎介; 藤原 真理奈; 野村 憲吾; 佐々木 祥平; 塩崎 雄治; 瀬川 博子; 辰巳 佐和子; 宮本 賢一  日本衛生学雑誌  67-  (4)  464  -471  2012/09
• カドミウム汚染によるリン代謝異常・骨軟化症発症機序の検討

  木戸慎介; 藤原真理奈; 瀬川博子; 辰巳佐和子; 宮本賢一  日本骨代謝学会学術集会プログラム抄録集  30th-  193  -193  2012/07
• 生体内リン代謝調節機構における唾液腺の関与

  向井朋; 瀬川博子; 森絢加; 四宮亜紀; 大西沙織; 佐々木祥平; 桑原頌治; 堀場直; 上田乙也; 寺社下浩一; 福島直; 石川康子; 木戸慎介; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  66th-  168  -168  2012/04
• 慢性腎臓病患者におけるFGF23産生亢進の分子機能解析

  木戸慎介; 藤原真理奈; 向井朋; 瀬川博子; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  66th-  152  -152  2012/04
• 骨細胞と腎臓を結ぶリン代謝調節機序

  辰巳佐和子; 釜谷達哉; 山口誠一; 野村憲吾; 吉見文子; 木戸慎介; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  66th-  168  -168  2012/04
• カドミウム汚染によるリン代謝異常:骨軟化症発症機序およびバイオマーカーの探索

  藤原真理奈; 木戸慎介; 瀬川博子; 辰巳佐和子; 宮本賢一  四国医学雑誌  68-  (1/2)  88  -88  2012/04
• The physiological roles of intestinal and renal phosphate transporters : an update

  KUWAHARA Shoji; OHI Akiko; NOMURA Kengo; TATSUMI Sawako; KIDO Shinsuke; SEGAWA Hiroko; MIYAMOTO Ken-ichi  消化と吸収  34-  (3)  181  -190  2012/03
• 近位尿細管上皮細胞における細胞密度を介したNa⁺依存性無機リン酸輸送担体Npt2aおよびNpt2cの発現調節機構

  塩崎雄治; 木戸慎介; 辰巳佐和子; 伊藤美紀子; 杉野紗貴子; 大井彰子; 瀬川博子; 宮本賢一  日本分子生物学会年会プログラム・要旨集(Web)  35th-  2P-0310 (WEB ONLY)  2012
• 肝臓切除後の低リン血症発症機構の解明

  野村憲吾; 辰巳佐和子; 宮川淳美; 岡奈都紀; 木戸慎介; 瀬川博子; 宮本賢一  日本栄養・食糧学会中国・四国支部大会講演要旨集  45th-  20  2012
• FGF23/Klotho研究の進歩 3 FGF23の作用と作用機序

  木戸慎介; 桑原頌治; 野村憲吾; 大井彰子; 辰巳佐和子; 瀬川博子; 宮本賢一  季刊腎と骨代謝  25-  (1)  25  -31  2012/01
• 肝臓切除による低リン血症発症メカニズムの解明

  野村憲吾; 辰巳佐和子; 山口誠一; 塩崎雄治; 菅生陵馬; 木戸慎介; 瀬川博子; 宮本賢一  季刊腎と骨代謝  24-  (4)  318  -318  2011/10
• カドミウムによるFibroblast growth factor 23(FGF23)発現調節機序の検討

  藤原真理奈; 木戸慎介; 荒波史; 中川航司; 瀬川博子; 辰巳佐和子; 宮本賢一  季刊腎と骨代謝  24-  (4)  320  -320  2011/10
• Hereditary hypophosphatemic rickets with hypercalciuria(HHRH)やFanconi’s syndromeにおける低リン血症の分子機構解明

  大西沙織; 大井彰子; 杉野紗貴子; 木戸慎介; 辰巳佐和子; 瀬川博子; 宮本賢一  日本腎臓学会誌  53-  (6)  797  -797  2011/08
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与

  木戸慎介; 藤原真理奈; 瀬川博子; 辰巳佐和子; 宮本賢一  日本骨代謝学会学術集会プログラム抄録集  29th-  194  -194  2011/07
• リン代謝におけるカルシウム受容体の役割

  辰巳佐和子; 菊井聡子; 野村憲吾; 斎藤友紀子; 塩崎雄治; 山口誠一; 木戸慎介; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  65th-  186  -186  2011/04
• 慢性腎臓病における食事リンによる腸管ペプチドトランスポーター調節

  瀬川博子; 古谷順也; 桑原頌治; 辰巳佐和子; 木戸慎介; 宮本賢一  日本栄養・食糧学会大会講演要旨集  65th-  192  -192  2011/04
• イタイイタイ病に見られる腎障害の発症・進展におけるFGF23の関与

  木戸慎介; 藤原真理奈; 中川航司; 瀬川博子; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  65th-  187  2011/04
• 糖尿病合併症発症におけるFGF23/Klothoの関与

  橋本由衣; 木戸慎介; 藤原真理奈; 瀬川博子; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会中国・四国支部大会講演要旨集  44th-  26  2011
• FGF23/Klothoを介した新たな腎尿細管リン・カルシウム代謝調節機構の解明

  坂田 雅映; 木戸 慎介; 橋本 由衣; 辰巳 佐和子; 瀬川 博子; 松本 俊夫; 宮本 賢一  日本病態栄養学会誌  13-  (5)  147  -147  2010/11
• 腸管とリン代謝

  宮本賢一; 花房悦代; 辰巳佐和子; 木戸慎介; 瀬川博子  日本骨代謝学会学術集会プログラム抄録集  28th-  128  -128  2010/07
• イタイイタイ病に見られるCd骨症(骨軟化症)の発症・進展におけるFGF23の関与

  木戸慎介; 中川航司; 橋本由衣; 坂田雅映; 辰巳佐和子; 荒波史; 瀬川博子; 宮本賢一  日本骨代謝学会学術集会プログラム抄録集  28th-  203  -203  2010/07
• リン酸輸送担体遺伝子欠損マウスの病態解析

  齋藤友紀子; 辰巳佐和子; 野村憲吾; 菊井聡子; 山口誠一; 塩崎雄治; 金子一郎; 瀬川博子; 木戸慎介; 宮本賢一  日本栄養・食糧学会大会講演要旨集  64th-  104  -104  2010/05
• ビタミンDによるリン代謝調節機序の解明

  金子一郎; 瀬川博子; 古谷順也; 桑原頌治; 荒波史; 富永理恵子; 花房悦世; 辰巳佐和子; 木戸慎介; 加藤茂明; 宮本賢一  日本栄養・食糧学会大会講演要旨集  64th-  104  -104  2010/05
• 副甲状腺ホルモン(PTH)によるリン代謝調節機構の解明

  大井彰子; 富永理恵子; 伊藤美紀子; 西山俊; 杉野紗貴子; 木戸慎介; 辰巳佐和子; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  64th-  118  -118  2010/05
• イタイイタイ病に見られる骨障害の発症・進展におけるFGF23の関与

  藤原真理奈; 木戸慎介; 坂田雅映; 荒波史; 瀬川博子; 辰巳佐和子; 宮本賢一  日本栄養・食糧学会中国・四国支部大会講演要旨集  43rd-  17  -18  2010
• 寿命調節因子Klothoによるリン代謝調節

  大井 彰子; 西山 俊; 伊藤 美紀子; 杉野 紗貴子; 木戸 慎介; 辰巳 佐和子; 瀬川 博子; 宮本 賢一  日本病態栄養学会誌  12-  (5)  187  -187  2009/12
• Mechanical stress enhances osteoblast differentiation via canonical Wnt pathway

  S. Kido; R. Kuriwaka; I. Endo; Y. Ito; T. Matsumoto  BONE  44-  S28  -S28  2009/05
• 老化関連因子klothoによるリン代謝調節機構の解明

  西山俊; 伊藤美紀子; 大井彰子; 杉野紗貴子; 坂田雅映; 蒲原彰宏; 木戸慎介; 辰巳佐和子; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  63rd-  215  -215  2009/05
• 2つのリン酸輸送体分子による生体内リン代謝調節機構の解明

  伊藤美紀子; 蒲原彰宏; 大井彰子; 西山俊; 杉野紗貴子; 坂田雅映; 辰巳佐和子; 木戸慎介; 瀬川博子; 宮本賢一  日本栄養・食糧学会大会講演要旨集  63rd-  215  -215  2009/05
• Bone Is More Susceptible to Vitamin K Deficiency than Liver.

  A. Kuwabara; K. Tanaka; N. Tsugawa; M. Kamao; M. Himeno; Y. Ogawa; M. Kishimoto; M. Fukuda; S. Kido; T. Okano  JOURNAL OF BONE AND MINERAL RESEARCH  23-  S321  -S321  2008/09
• Bone Marrow Stromal Cells Up-regulate M-CSF Receptor in Monocytes to Disrupt Dendritic Cell Differentiation While Facilitating Osteoclastogenesis in Myeloma.

  M. Abe; M. Hiasa; A. Oda; H. Amou; K. Takeuchi; O. Tanaka; S. Nakamura; H. Miki; K. Kagawa; K. Yata; S. Ozaki; S. Kido; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  23-  S301  -S301  2008/09
• TGF-beta Suppresses Adipocytic Differentiation and Enhances Accumulation of Stromal Cells in Myeloma Bone Lesions

  K. Takeuchi; M. Abe; M. Hiasa; O. Tanaka; S. Nakamura; H. Miki; K. Kagawa; K. Yata; T. Hashimoto; S. Ozaki; S. Kido; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  23-  S189  -S189  2008/09
• Coactivator MBF1 Binds to JunD and Protects Its Transcriptional Activity Against Oxidative Stress to Prevent Age-Related Suppression of Osteoblast Differentiation

  S. Kido; R. Kuriwaka; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  23-  S70  -S70  2008/09
• TGF‐β阻害薬による骨芽細胞分化誘導は骨髄腫腫瘍増殖を抑制する

  竹内恭子; 安倍正博; 日浅雅博; 田中修; 藤井志朗; 中村信元; 三原愛; 三木浩和; 浅野仁; 賀川久美子; 北添健一; 矢田健一郎; 橋本年弘; 尾崎修治; 木戸慎介; 松本俊夫  臨床血液  48-  (9)  872  -872  2007/09
• Up-regulation of TACE in monocytes ameliorates their deflected differentiation into osteoclasts and dendritic cells in myeloma

  M. Abe; M. Hiasa; S. Kido; K. Takeuchi; K. Kitazoe; A. Oda; H. Amou; K. Kagawa; T. Hashimoto; S. Ozaki; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  22-  S189  -S189  2007/09
• TGF-beta inhibition suppresses myeloma cell growth via enhancement of osteoblast differentiation

  K. Takeuchi; M. Abe; A. Oda; H. Amou; M. Hiasa; O. Tanaka; S. Fujii; S. Nakamura; A. Mihara; H. Miki; J. Asano; K. Kagawa; K. Kitazoe; K. Yata; T. Hashimoto; S. Ozaki; S. Kido; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  22-  S295  -S295  2007/09
• Up-regulation of tace in monocytes disrupts myeloma cell-induced osteoclastogenesis and induces myeloid dendritic cell differentiation

  M. Abe; M. Hiasa; S. Kido; A. Oda; H. Amou; S. Fujii; O. Tanaka; A. Mihara; H. Miki; J. Asano; K. Kagawa; K. Takeuchi; K. Kitazoe; T. Hashimoto; S. Ozaki; T. Matsumoto  HAEMATOLOGICA-THE HEMATOLOGY JOURNAL  92-  (6)  133  -133  2007/06
• TGF-bera inhibition restores bone formation to suppress tumor growth in myeloma

  K. Takeuchi; M. Abe; A. Oda; H. Amou; S. Fujii; O. Tanaka; M. Hiasa; A. Mihara; H. Miki; J. Asano; K. Kagawa; K. Kitazoe; T. Hashimoto; S. Ozaki; S. Kido; T. Matsumoto  HAEMATOLOGICA-THE HEMATOLOGY JOURNAL  92-  (6)  133  -133  2007/06
• 骨芽細胞分化の誘導による骨髄腫細胞の増殖抑制

  竹内恭子; 安倍正博; 日浅雅博; 田中修; 藤井志朗; 三原愛; 三木浩和; 浅野仁; 賀川久美子; 北添健一; 橋本年弘; 尾崎修治; 木戸慎介; 松本俊夫  日本骨代謝学会学術集会プログラム抄録集  25th-  199  -199  2007/06
• GM-CSFとIL-4は単球のM-CSF破骨細胞分化を抑制し樹状細胞分化を誘導する

  日浅 雅博; 安倍 正博; 橋本 年弘; 尾崎 修治; 井上 大輔; 木戸 慎介; 森山 啓司; 松本 俊夫  日本骨形態計測学会雑誌 = Journal of Japanese Society of Bone Morphometry  16-  (3)  66  -66  2006/12
• SB431542, a TGF-Beta receptor kinase inhibitor, restores bone formation which ameliorates myeloma-induced microenvironment.

  Kyoko Takeuchi; Masahiro Abe; Asuka Oda; Hiroe Amou; Masahiro Hiasa; Jin Asano; Kenichi Kitazoe; Toshihiro Hashimoto; Shuji Ozaki; Shinsuke Kido; Daisuke Inoue; Toshio Matsumoto  BLOOD  108-  (11)  992A  -992A  2006/11  [Refereed]
  
• Expression profiling by quantitative and large scale proteomics in differentiating osteoblasts

  T. Miyamoto; S. Kido; M. Abe; T. Matsumoto; H. Taniguchi  MOLECULAR & CELLULAR PROTEOMICS  5-  (10)  S375  -S375  2006/10
• TGF‐β阻害剤は骨形成を回復し骨髄腫細胞の増殖を抑制する

  竹内恭子; 安倍正博; 木戸慎介; 日浅雅博; 長樂雅仁; 浅野仁; 賀川久美子; 北添健一; 橋本年弘; 尾崎修治; 井上大輔; 松本俊夫  臨床血液  47-  (9)  1050  -1050  2006/09
• GM-CSF and IL-4 enhance dendrocyte differentiation and inhibit osteoclastogenesis by ectodomain shedding of M-CSF receptor in monocytes.

  M. Hiasa; M. Abe; T. Hashimoto; S. Ozaki; S. Kido; D. Inoue; H. Amou; A. Oda; K. Moriyama; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  21-  S263  -S263  2006/09
• Enhancement of osteoblast differentiation by inhibition of TGF-beta signaling suppresses myeloma cell growth and protects from destructive bone lesions.

  K. Takeuchi; M. Abe; A. Oda; H. Amou; M. Hiasa; J. Asano; K. Kitazoe; S. Kido; D. Inoue; T. Hashimoto; S. Ozaki; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  21-  S28  -S28  2006/09
• BMP-2 enhances mechanical stress-induced Osteobalstic differentiation via formation of Smad1/Delta-FosB/JunD complex on IL-11 gene promoter.

  S. Kido; R. Kuriwaka; T. Miyamoto; H. Taniguchi; T. Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  21-  S371  -S371  2006/09
• TGF‐β阻害薬による骨髄腫における骨形成の誘導

  竹内恭子; 安倍正博; 日浅雅博; 浅野仁; 北添健一; 橋本年弘; 尾崎修治; 木戸慎介; 井上大輔; 松本俊夫  日本骨代謝学会学術集会プログラム抄録集  24th-  172  -172  2006/07
• 力学的負荷による骨形成促進過程における転写因子群の機能解析

  木戸 慎介; 井上 大輔; 松本 俊夫  日本骨形態計測学会雑誌 = Journal of Japanese Society of Bone Morphometry  16-  (1)  32  -32  2006/04
• SB431542, a TGF-beta receptor kinase inhibitor, restores bone formation which disrupts myeloma-induced microenvironment

  K. Takeuchi; M. Abe; M. Hiasa; K. Kitazoe; T. Hashimoto; S. Ozaki; S. Kido; D. Inoue; T. Matsumoto  CANCER TREATMENT REVIEWS  32-  S25  -S25  2006
• Angiogenesis and osteoclastogenesis are mutually stimulated in myeloma: A role for VEGF and osteopontin.

  Y Tanaka; M Abe; M Hiasa; T Hashimoto; S Kido; D Inoue; S Ozaki; K Moriyama; T Matsumoto  BLOOD  106-  (11)  702A  -702A  2005/11
• Myeloma cell-derived MIP-1 suppresses dendritic cell maturation and induces aberrant osteoclastogenesis from immature dendritic cells.

  T Hashimoto; M Abe; M Hiasa; J Asano; Y Tanaka; E Sekimoto; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  20-  (9)  S212  -S213  2005/09
• Targeting myeloma bone marrow microenvironment by gammadeltaT cells.

  M Abe; T Hara; H Shibata; T Hashimoto; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  20-  (9)  S32  -S32  2005/09
• Glucocorticoid blocks AP-1 activity leading to transcriptional repression of an osteogenic cytokine interleukin-11: A mechanism of impaired bone formation

  Y Ito; S Kido; D Inoue; T Matsumoto  BONE  36-  S127  -S127  2005/06
• 力学的負荷による骨芽細胞の分化誘導因子の転写制御

  木戸慎介  腎と骨代謝  18-  (1)  31  -38  2005
• Myeloma cells reciprocally regulate osteoclast and dendritic cell differentiation from monocytes

  T Hashimoto; M Abe; Y Tanaka; E Sekimoto; T Oshima; H Shibata; S Ozaki; S Kido; D Inoue; T Matsumoto  CANCER TREATMENT REVIEWS  31-  S37  -S37  2005
• Myeloma cells suppress osteoblast differentiation by secreting a soluble Wnt inhibitor, sFRP-2.

  T Oshima; M Abe; J Asano; T Hara; K Kitazoe; E Sekimoto; Y Tanaka; H Shibata; T Hashimoto; S Ozaki; S Kido; D Inoue; T Matsumoto  BLOOD  104-  (11)  648A  -648A  2004/11
• Reciprocal regulation of osteoclast and dendritic cell differentiation from monocytes by myeloma cells: A role for MIP-1

  T Hashimoto; M Abe; Y Tanaka; E Sekimoto; T Oshima; H Shibata; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  19-  S359  -S359  2004/10
• Wnt10b expression in bone marrow stromal cells are regulated by sex steroids

  T Hayashi; S Kido; D Inoue; T Ishikawa; T Matsumoto; R Okazaki  JOURNAL OF BONE AND MINERAL RESEARCH  19-  S407  -S407  2004/10
• A novel mechanical stress-induced signaling pathway leading to protein kinase C delta-dependent Smad1 activation in osteoblasts.

  S Kido; D Inoue; T Imamura; K Miyazono; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  19-  S257  -S257  2004/10
• Myeloma cells suppress osteoblast differentiation by secreting a soluble wnt inhibitor, sFRP-2

  T Oshima; M Abe; E Sekimoto; Y Tanaka; H Shibata; T Hashimoto; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  19-  S65  -S65  2004/10
• Inhibition of interleukin-11 gene transcription by glucocorticoid.

  Y Ito; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  19-  S200  -S201  2004/10
• Myeloma cells express BMP-2 and Wnt antagonists: A mechanism of impaired bone formation in multiple myeloma

  T Oshima; N Abe; T Hashimoto; H Shibata; E Sekimoto; Y Tanaka; K Kitazoe; T Hara; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  19-  (9)  1581  -1581  2004/09
• Myeloma-bone interaction for the development of myeloma bone disease

  T Matsumoto; S Kido; D Inoue; T Oshima; M Abe  JOURNAL OF BONE AND MINERAL RESEARCH  19-  (9)  1566  -1566  2004/09
• Glucocorticoid action in osteoblasts

  木戸 慎介; 井上 大輔; 松本 俊夫  ホルモンと臨牀  52-  58  -62  2004/03
• Protein kinase C-dependent but BMP-2 receptor-independent activation of Smad1/5 by fluid shear stress in osteoblasts

  D Inoue; S Kido; T Imamura; K Miyazono; T Matsumoto  BONE  34-  S7  -S8  2004
• 骨髄腫細胞はBMP-2による, 骨芽細胞分化の促進を抑制する

  大島 隆志; 安倍 正博; 関本 悦子; 田中 洋一; 柴田 泰伸; 橋本 年弘; 尾崎 修治; 木戸 慎介; 井上 大輔; 松本 俊夫  日本骨形態計測学会雑誌 = Journal of Japanese Society of Bone Morphometry  13-  (3)  56  -56  2003/12
• Myeloma cells express BMP-2 and Wnt antagonists: A mechanism of impaired bone formation in multiple myeloma.

  T Oshima; M Abe; T Hashimoto; H Shibata; E Sekimoto; T Tanaka; K Kitazoe; T Hara; S Ozaki; S Kido; D Inoue; T Matsumoto; M Kosaka  BLOOD  102-  (11)  930A  -930A  2003/11
• Functional RANK ligand expression in malignant B-lymphoid cells.

  H Shibata; M Abe; T Hashimoto; T Ohshima; J Asano; T Hara; E Sekimoto; Y Tanaka; K Kitazoe; A Jalili; S Ozaki; S Kido; D Inoue; M Kosaka; T Matsumoto  BLOOD  102-  (11)  274B  -274B  2003/11
• Osteoclasts enhance angiogenesis in concert with myeloma cells through osteopontin and VEGF.

  M Abe; T Hashimoto; T Oshima; H Shibata; E Sekimoto; Y Tanaka; K Kitazoe; T Hara; J Asano; A Jalili; S Kido; D Inoue; S Ozaki; M Kosaka; T Matsumoto  BLOOD  102-  (11)  443A  -443A  2003/11
• Myeloma cells suppress BMP-2-mediated osteoblast differentiation: Impaired bone formation in multiple myeloma.

  T Oshima; M Abe; T Hara; K Kitazoe; E Sekimoto; Y Tanaka; H Shibata; T Hashimoto; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S309  -S309  2003/09
• Osteoclasts enhance angiogenesis in concert with myeloma cells through osteopontin and VEGF.

  M Abe; T Hashimoto; T Oshima; H Shibata; E Sekimoto; Y Tanaka; T Hara; K Kitazoe; S Ozaki; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S37  -S37  2003/09
• A novel mechanical stress-induced signaling pathway leading to Smad1/5/8 activation in osteoblasts.

  S Kido; D Inoue; T Imamura; K Miyazono; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S217  -S217  2003/09
• Regulation of c-Fos protein expression in osteoclast lineage cells: Involvement of ubiquitin/proteasome pathway.

  Y Ito; D Inoue; S Kido; Endo, I; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S235  -S235  2003/09
• Androgen acts like estrogen on the differentiation of the bone marrow stromal cells.

  T Hayashi; S Kido; D Inoue; H Tanaka; T Matsumoto; R Okazaki  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S344  -S344  2003/09
• Transcriptional induction of FosB/DeltafosB gene by mechanical stress in osteoblasts.

  D Inoue; S Kido; S Kato; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  18-  S72  -S72  2003/09
• Interleukin-11 is an osteogenic cytokine that inhibits osteoblast apoptosis: Up-regulation of BCL-2 and synergism with estrogen

  S Kido; D Inoue; S Kato; K Yoshida; T Matsumoto  BONE  32-  (5)  S90  -S91  2003/05
• Myeloma cells suppress osteoblast differentiation: Impaired bone formation in multiple myeloma

  T Oshima; M Abe; T Hashimoto; H Shibata; E Sekimoto; Y Tanaka; S Ozaki; S Kido; D Inoue; T Matsumoto  BONE  32-  (5)  S129  -S129  2003/05
• Androgens exert estrogen-like effects on the differentiation of bipotential bone marrow stromal cells

  T Hayashi; S Kido; D Inoue; H Tanaka; Y Sakamoto; T Matsumoto; R Okazaki  BONE  32-  (5)  S147  -S147  2003/05
• Transcriptional induction of FOSB/DELTAFOSB gene by fluid shear stress in osteodlasts

  D Inoue; S Kido; Y Ito; T Matsumoto  BONE  32-  (5)  S83  -S83  2003/05
• Osteoclasts enhance myeloma growth and survival: A vicious cycle between bone destruction and myeloma expansion

  M Abe; T Hashimoto; H Shibata; T Oshima; E Sekimoto; Y Tanaka; S Ozaki; S Kido; D Inoue; T Matsumoto  BONE  32-  (5)  S90  -S90  2003/05
• Cellular interplays between myeloma and bone cells enhance myeloma expansion and bone resorption while suppressing bone formation.

  M Abe; T Hashimoto; T Oshima; H Shibata; S Ozaki; A Shioyasono; Y Tanimoto; K Hiura; K Moriyama; S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  17-  S229  -S229  2002/09
• Mechanism of mechanical stress-induced activation of AP-1/IL-11 transcriptional cascades.

  D Inoue; S Kido; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  17-  S183  -S183  2002/09
• Down-regulation of interleukin-11 may be involved in the pathogenesis of glucocorticoid-induced osteoporosis.

  S Kido; D Inoue; S Kato; Y Ito; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  17-  S134  -S134  2002/09
• MECHANISM OF OSTEOLYSIS BY MULTIPLE MYELOMA

  ABE M.; HIURA K.; HASHIMOTO T.; KIDO S.; INOUE D.; OZAKI S.; KOSAKA M.; MATSUMOTO T.  Journal of bone and mineral metabolism  19-  93  -93  2001/11
• The effect of periostin on osteoclast differentiation and activation.

  J Wilde; K Hiura; M Yokozeki; S Kido; D Inoue; T Matsumoto; A Kudo; K Moriyama  JOURNAL OF BONE AND MINERAL RESEARCH  16-  S381  -S381  2001/09
• AP-1/interleukin (IL)-11 signaling cascades may be involved in PTH-induced bone formation: ERK-dependent induction of delta-fosB and IL-11 by hPTH(1-34).

  S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  16-  S175  -S175  2001/09
• Osteoclasts stimulate myeloma cell growth through direct cellular interactions via production of osteopontin and interleukin (IL)-6.

  M Abe; D Inoue; T Hashimoto; S Kido; Y Shibata; T Oshima; S Ozaki; K Hiura; K Moriyama; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  16-  S182  -S182  2001/09
• Activation of a Ca/ERK/delta-fosB(AP-1) cascade by mechanical stress in osteoblasts, leading to up-regulation of an osteogenic cytokine, interleukin (IL)-11.

  S Kido; D Inoue; E Tohjima; S Kato; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  16-  S202  -S202  2001/09
• Interactions between multiple myeloma and bone cells forming a vicious cycle

  M Abe; K Hiura; J Wilde; S Kido; S Hashimoto; S Ozaki; K Moriyama; D Inoue; T Matsumoto  BONE  28-  (5)  S81  -S81  2001/05
• Potental roles for AP-1/interleukin-11 pathways in mechanical stress-induced bone formation

  S Kido; D Inoue; E Tohjima; T Matsumoto  BONE  28-  (5)  S85  -S85  2001/05
• Estrogen inhibits adipocytic differentiation of bone marrow stromal cells through either estrogen receptor alpha or beta

  R Okazaki; D Inoue; M Shibata; M Saika; S Kido; Y Sakamoto; T Matsumoto  BONE  28-  (5)  S78  -S79  2001/05
• Fos family transcription factors as critical components of osteogenic signalling elicited by mechanical loading.

  D Inoue; S Kido; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  15-  S376  -S376  2000/09
• Stimulation of myeloma cell growth and survival by osteoclasts: Formation of a vicious cycle

  M Abe; K Hiura; J Wilde; T Hashimoto; S Ozaki; S Kido; D Inoue; K Moriyama; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  15-  S176  -S176  2000/09
• Estrogen potentiates bone morphogenetic protein-2 mediated early osteoblastic differentiation in both estrogen receptor (ER) alpha and ER beta overexpressing stromal cell lines.

  R Okazaki; D Inoue; M Saika; S Kido; Y Sakamoto; K Tanaka; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  15-  S238  -S238  2000/09
• Expression of RANK is dependent upon differentiation into the macrophage/osteoclast lineage: Induction by 1, 25(OH)2D3 and TPA in a human cell line, HL-60.

  S Kido; D Inoue; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  15-  S391  -S391  2000/09
• Identification of regulatory sequences and binding proteins in the type II sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate

  S Kido; K Miyamoto; H Mizobuchi; Y Taketani; Ohkido, I; N Ogawa; Y Kaneko; S Harashima; E Takeda  JOURNAL OF BIOLOGICAL CHEMISTRY  274-  (40)  28256  -28263  1999/10
• 大豆由来イソフラボンによる骨代謝調節機序

  森田 恭子; 濱松 由子; 木戸 慎介  大豆たん白質研究  2-  (20)  76  -82  1999/10
• 17 beta-estradiol stimulates expression of osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) by a mouse stromal cell line, ST-2.

  M Saika; D Inoue; S Kido; T Matsumoto  JOURNAL OF BONE AND MINERAL RESEARCH  14-  S232  -S232  1999/09
• Mechanism of the intestine spesific expression of vitamin D receptor gene

  YAMAMOTO Hironori; KITANO Mutsuko; KIDO Shinsuke; TAKETANI Yutaka; MORITA Kyoko; MIYAMOTO Ken-ichi; PIKE John Wesley; TAKEDA Eiji  日本分子生物学会年会プログラム・講演要旨集  21-  424  -424  1998/12
• Developmental change of Na/Pi cotransporters expression and renal immaturation by low-phosphate diet

  FUJIOKA A; MORITA K; KIDO S; TAKETANI Y; MIYAMOTO K; TAKEDA E  日本先天代謝異常学会雑誌  14-  (2)  246  -246  1998/10
• Molecular and Cellular Regulation of Renal Phosphate Transporters in X-Linked Hypophosphatemia

  MIYAMOTO Ken-ichi; TAKETANI Yutaka; MORITA Kyoko; SEGAWA Hiroko; NII Tomoko; FUJIOKA Ai; KIDO Shinsuke; ARAI Hidekazu; TANI Yoshiko; KATAI Kanako; TATUMI Sawalp; TAKEDA Eiji  Clinical and experimental nephrology  2-  (3)  178  -182  1998/09
• 腎臓のリン応答性転写調節因子の検索

  木戸 慎介; 小川 暢男; 水渕 裕之; 竹谷 豊; 宮本 賢一; 森田 恭子; 原島 俊; 武田 英二  日本骨代謝学会雑誌 = Japanese journal of bone metabolism  16-  (2)  77  -77  1998/07
• Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D3: Identification of a vitamin D- responsive element in the human NAPI-3 gene

  Yutaka Taketani; Hiroko Segawa; Mika Chikamori; Kyoko Morita; Keiko Tanaka; Shinsuke Kido; Hironori Yamamoto; Yuka Iemori; Sawako Tatsumi; Naoko Tsugawa; Toshio Okano; Tadashi Kobayashi; Ken-Ichi Miyamoto; Eiji Takeda  Journal of Biological Chemistry  273-  (23)  14575  -14581  1998/06
• リンの感受性とその機構

  腎と骨代謝  11(1),61-68-  1998
• Identification of VDRE in the human sodium dependent phosphate transporter gene.

  Y Taketani; K Miyamoto; M Chikamori; K Tanaka; H Segawa; S Kido; K Morita; E Takeda  JOURNAL OF BONE AND MINERAL RESEARCH  12-  F421  -F421  1997/08
• 2-I-24 ヒトリン輸送担体遺伝子の転写調節領域におけるビタミンD応答配列の同定 : 第49回大会一般研究発表要旨

  竹谷 豊; 近森 水香; 田中 佳子; 山本 浩範; 木戸 慎介; 宮本 賢一; 森田 恭子; 武田 英二  ビタミン  71-  (4)  199  -199  1997/04
• ビタミンDによるNa/リン共輸送担体遺伝子発現調節

  竹谷 豊; 近森 水香; 田中 佳子; 山本 浩範; 木戸 慎介; 森田 恭子; 宮本 賢一; 武田 英二  日本分子生物学会年会プログラム・講演要旨集  19-  510  -510  1996/08

Awards & Honors

• 2018/03 食事療法学会 優秀演題賞
   

  受賞者: 木戸 慎介
• 2002 日本骨代謝学会奨励賞
   JPN
• 2002 Young Investigate, Award (ASBMR)
  
• 2002 American Society for Bone and Mineral Research (ASBMR) Young Investigator's Award
   

  受賞者: KIDO Shinsuke
• 2001 日本骨代謝学会 優秀演題賞
   

  受賞者: 木戸 慎介

Research Grants & Projects

• 慢性腎臓病患者を対象とした栄養補助食品（低リン食品）の新規開発に向けた基礎的研究

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2023/04 -2026/03 

  Author : 木戸 慎介
• Improvement of QOL on diet therapy at home based on Augmented Reality and Food Big Data Analysis

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015/04 -2017/03 

  Author : Kato Hirokazu; KANAYA Shigehiko; Sandor Christian; YAMAMOTO Goshiro; TAKETOMI Takafumi; KIDO Shinsuke; INAMURA Maya; UENISHI Kozue

   

  We confirmed the importance of examining the menu of restricted diet while paying attention to micronutrients by utilizing the nutrient database we developed. Furthermore, we confirmed that adjusting nutritional constraints in multiple days is effective for improving patients' QOL by using our menu recommendation system. In order to introduce tablet type augmented reality technology into such a recommendation system, we also examined to evaluate its usefulness as a user interface, and established guidelines for the evaluation.
• New nutritional treatment strategies for chronic kidney disease for FGF23

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015 -2017 

  Author : KIDO Shinsuke

   

  Indoxyl sulfate (IS) as uremic toxins, is accumulated in the serum to CKD patients. However, the relationship to between rise in serum FGF23 and IS has not been elucidated. The present study was undertaken to examine the effects of IS on FGF23 production in rat osteosarcoma UMR-106 cells. We obtained following findings: (1) The up-regulation of GalNAc-T3 by IS suppress proteolytic processing of FGF23 and probably stimulates the elevation of serum FGF23; (2) We investigated effect of an ethanol-extract from several vegetables on the FGF23 production in UMR106 cells. As a result, the production of FGF23 by IS was inhibited by addition of the ethanol extracts from Broccoli sprout (Brassica oleracea var. italica) and mulukhiya (Corchorus olitorius). Our finding could contributes to develop the FGF23-targeting the development of diet therapy for CKD.
• Muscle atrophy in patients with CKD results from FGF23/klotho-mediated suppression of Insulin/IGF-I signaling

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2012 -2014 

  Author : KIDO Shinsuke

   

  Muscle atrophy is a significant consequence of CKD that increases a patient’s risk of mortality and decrease their QOL. In these patients, the circulation levels of FGF23 are significantly increased, but the relationship between FGF23 and muscle atrophy are not clear. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klotho induced muscle atrophy. As a results, we found that AGEs, an accumulated in patients with CKD, increases shedding of Klotho in kidney cells. Moreover, we demonstrated that both FGF23 and sKlotho inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-1 signaling. These observations suggested a divergent role of FGF23 and sKlotho in the regulation of skeletal muscle differentiation and thereby muscle atrophy under the pathological conditioned in CKD patients.
• Signal networks among organ/tissue in the disorder of phosphate homeostasis

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2011 -2013 

  Author : MIYAMOTO KENICHI; SEGAWA Hiroko; KIDO Shinsuke

   

  Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays an important role in phosphate (Pi) transport in the proximal tubular cells. Klotho forms a specific receptor complex with FGF receptor that transmits signaling of FGF23 in the distal tubules. FGF23/klotho signaling leads to down-regulation of sodium-dependent Pi cotransporter (NaPi-II ) in the proximal tubules. In the present study, we investigated the mechanisms of down-regulation of renal Pi transporter by FGF23/klotho system and the production of FGF23 in bone cells. We show that klotho expression in the proximal tubules is induced by several conditions. Furthermore, inactivation of NaPi-IIc by PKC is the first step of FGF23/klotho dependent down-regulation of the transporters. Thus, FGF23/klotho signaling in the kidney-bone axis is essential for Pi homeostasis.
• The systemic NAD world in chronic kidney disease

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2011 -2013 

  Author : TATSUMI Sawako; KIDO Shinsuke

   

  This study determines the presence of the new phosphate(Pi)metabolic pathway through the nicotinamide phosphoribosyltransferase(Nampt)as the first rate-limiting enzyme in converting NAM to NAD.The activation of Nampt caused the significantly increased levels of urinary Pi excretion and the decreased levels of intestinal Pi absorption.The present data suggest that the cause of hypophosphatemia and hyperphosphaturia observed after 70% hepatectomy is caused by abnormal Nampt/NAM activation in the liver and kidney. These result shows presence of the liver-kidney axsis in Pi metabolism. We examine a mechanism to do constantly the Pi/Ca ratio through Nampt.We think these research may be contribute to the prevention of cardiovascular disease development of patients with chronic renal disease.
• Involvement of anti-aging factor in the pathogenesis of senile osteoporosis and vascular calcification

  Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(若手研究(B))

  Date (from‐to) : 2009 -2011 

  Author : Shinsuke KIDO

   

  Oxidative stress reduces osteoblast number and suppresses bon formation, leading to the age-related loss of bone. We have demonstrated that anti-adipogenic cytokine, IL-11, is expressed in osteoblasts in an AP-1-dependent manner, and that DNA binding activity of JunD was reduced without change in its protein level in aged mice. Therefore, there is a possibility that reduced JunD activity may be caused by post-translational modification of JunD by an age-related increase in oxidative stress. In the present study, we showed that MBF1 protein was expressed in all tissues examined, whereas the amount of MBF1 decreased in many tissues including bone of aged mice. Besides, DNA precipitation assay demonstrated that MBF1 forms complex with JunD on an AP-1 site of IL-11 promoter via binding to a basic region of JunD. MBF1 binding to JunD also enhanced AP-1-dependnt IL-11 gene transcription even in the presence of hydrogen peroxide. It is suggested that reduced MBF1 protein expression in osteoblasts may play a role in age-related impairment of osteoblast differentiation by suppressing IL-11 transcription via a reduction in JunD activity, and that MBF1 can be a new target against age-related loss of bone.
• Molecular mechanic sum of the regulation and dies regulation of bone homeostasis and Development of therapeutic approaches

  Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(A))

  Date (from‐to) : 2005 -2007 

  Author : Toshio MATSUMOTO; 井上 大輔; Masahiro ABE; Masashi AKAIKE; Shinsuke KIDO

   

  In order to clarify the regulatory mechanisms for maintaining structural and functional homeostasis of skeletal system, as well as to elucidate the molecular mechanisms for the development of disorders caused by disruption of the skeletal homeostatic system, the present study was conducted in the following three areas :(1) Elucidation of the mechanism of bone formation and the pathogenesis of disorders due to impaired bone formation: We have identified ΔFosB as an early response gene to mechanical load to the bone (JBMR'04). Rapidly induced ΔFosB forms heterodimers with JunD), and stimulated its target genes. IL-11 is one of the target genes, and ΔFosB /JunD heterodimer binds to a putative AP-1 site on the IL-11 gene promoter We also found that echanical stimuli enhances phosphorylation of Smadl via an activation of PECd without stimulation by BMP-2, and that phosphorylated Smadl forms complex with ΔFosB/JunD on the IL-11 gene promote fir full transcriptional activation of I-11 gene.(2) Elucidation of the pathogenic mechanisms 'for the destructive bone lesions by multiple myeloma: We have previously found that multiple myeloma enhances osteoclastic bone resorption via the production of MIP-1, a C-C chemokine. (Blood '02, '04) In the present study, we found that myeloma cells constitutively secrete sFRP-2, an inhibitor of Wnt signaling, which strongly inhibits osteoblast differentiation. In addition, TGF-β also suppressed terminal differentiation of osteoblasts. Because TGF-β is released from bone matrix by enhanced bone resorption, these results imply that there is a strong suppression ofbone formation in myeloma-bone microenvironment. If a TGF-β antagonist was added, the suppressed bone formation by myeloma cells was ameliorated, and the restoration of terminal osteoblastic differentiation markedly suppressed myeloma cell growth. These results are consistent with the notion that there is a vicious cycle in myeloma-bone microenvironment, in which myeloma cells enhance bone resorption and suppress bone formation to extend bone destruction, and myeloma cell-derived sFRP-2 as well as TGF-β released from the bone matrix by the enhanced bone resorption co-operatively suppress bone formation. Furthermore, the suppression of osteoblast maturation provides a suitable environment for myeloma cell growth which can be called "myeloma niche". Wnt inhibitors and TGF-β antagonists can be targets for the development of new therapeutic modalities.(3) Elucidation of the pathogenic mechanisms for disorders caused by disturbances in skeletal circulation: We have previously reported that glucocorticoid excess suppresses endothelium-dependent vasodilatory responses via a reduction in NO by an enhanced production of superoxides in the endothelium (Circ Res '03). We further found that glucocorticoid excess markedly suppresses urinary NOx excretion and aortic eNOS expression. In addition, pitavastatin antagonizes the effects of glucocorticoids. These observations support our hypothesis that glucocorticoid excess causes circulatory disturbances in microvessels of the femoral neck, which plays an important role in the development of idiopathic osteonecrosis of the femoral neck. Statins with high systemic blood levels can be a new candidate for the prevention of superoxide-induced circulatory disturbances.
• ヒト白血病細胞株HL-60の分化誘導に伴うRANKの発現と細胞内シグナル

  Date (from‐to) : 2000 -2003
• Fos family Transcription Factors as Critical Components of Osteogenic Signaling Elicited by Mechanical Loading.

  Date (from‐to) : 2000 -2003
• 力学的負荷による骨形成促進機構におけるfos family遺伝子の役割

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2001 -2002 

  Author : 木戸 慎介

   

  (研究結果の概要) 1.力学的負荷によるδfosB及びIL-11の発現誘導機構の解析 (1)力学的負荷によるδfosB及びIL-11の誘導はBAPTA並びにERK阻害薬(UO126)存在下ではほぼ完全に抑制された。従ってfluid shear stress (FSS)による両者の誘導はCa及びERKに依存することが示された。また各々のプロモーター領域を用いたluciferase assayによる解析から、δfosB/IL-11の誘導は転写段階であること、さらにδfosBはAP-1配列を介してIL-11遺伝子の転写活性を促進することを明らかにした。 2.力学的負荷並びにIL-11の生物学的作用(In vitro) (1)新生児マウス頭蓋骨由来の初代培養系骨芽細胞(POB)において、troglitazoneは脂肪細胞分化を誘導したが、この作用は間欠的なFSS刺激(10分/時間)を断続的に与えることでほぼ半分に抑制された。またこの作用はIL-11中和抗体により解除された。 (2)同様の細胞系でFSSあるいはIL-11はdexamethasone (Dex)によるアポトーシスを抑制すること、さらにFSSの有する抗アポトーシス作用はIL-11作用を介することを見いだした。 (3)IL-11はBcl-2の発現をmRNA、タンパクレベルで誘導することを見いだした。 3.In vivoでの解析 IL-11 transgenicマウスに対する尾部懸垂の効果を見たところ、重力免荷による骨量減少がIL-11の過剰発現により抑制される傾向が見られた。またDex投与による骨量減少に対しても同様であった。 (総括) 力学的負荷は骨芽細胞系においてAP-1(δfosB)/IL-11経路の活性化を介して生理的な骨形成並びに骨量を椎持していることが示唆された。本経路の解明は不動、あるいはステロイド過剰により惹起される骨量減少(骨粗鬆症)の病態解明並びにその有効な治療薬の解明につながるものと期待される。
• Expression of RANK is Dependent uppon Differentiation into the Macrophage/Osteoclast lineage ; Induction by 1.25(OH)₂D₃ and TPA in a human cell line, HL60

Social Contribution

• 奈良県栄養士会生涯教育研修会（講演タイトル：栄養診断、栄養診断演習）

  Date (from-to) : 2016/07/09

  Role : Lecturer

  Category : Qualification seminar

  Sponser, Organizer, Publisher  : 奈良県栄養士会
• 2016近畿大学農学部公開講座in東京（講演タイトル：あなたはリンを摂り過ぎていませんか？）

  Date (from-to) : 2016/05/14

  Role : Lecturer

  Category : Lecture

  Sponser, Organizer, Publisher  : 近畿大学農学部
• 奈良県栄養士会生涯教育研修会（講演タイトル：栄養ケアプロセスNCP)

  Date (from-to) : 2015/10/24

  Role : Lecturer

  Category : Qualification seminar

  Sponser, Organizer, Publisher  : 奈良県栄養士会
• 第12回市民公開講座（講演タイトル：知っておきたい食物とリンの話）

  Date (from-to) : 2015/07/18

  Role : Lecturer

  Category : Lecture

  Sponser, Organizer, Publisher  : 近畿大学アンチエイジングセンター

Others

• 2016/04 -2016/04  医食農連携を基盤とした慢性腎臓病（CKD)の新たな新たな食事療法の開発とその実践 

  近畿大学学内研究奨励金 研究種目：21世紀研究開発奨励金（共同研究助成金） 課題番号：KD07 研究内容：本研究ではCKDの病態悪化を阻止するために、外来患者の自宅での食事療法を良好に継続できる「在宅食事・栄養マネジメントシステム」を確立する。当該システムは、外来患者であっても入院患者と同等の包括的栄養ケアを受けられるシステムであり、その実現のために下記3項目の実践および検証を行う。 (1)持続可能な食事・栄養療法の実現に適した高機能食材の開発と育成 (2)ICT技術を基盤とした食事・栄養管理を容易にする在宅栄養ケア支援プログラムの開発 (3)外来患者を対象とした、包括的栄養ケアプログラムの実践とその有効性の検証 これら3項目を実現することで、CKD治療における外来診療と在宅ケア(自宅において患者自身が実践する食事療法)とのシームレス化を可能にする。そのことにより、CKD患者が健康な人と同等の質を有する日常生活（QOL向上）ならびに健康寿命の確保を目指す。

Other link

researchmap

https://researchmap.jp/read0194429