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Regulation of osteoblastic differentiation and its implication in involutional osteoporosis

Research Project

Project/Area Number 07671111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionUniversity of Tokyo

Principal Investigator

TAKEUCHI Yasuhiro  University of Tokuo, Faculty of Medicine, Assistant Professor, 医学部・附属病院(分), 助手 (50202164)

Co-Investigator(Kenkyū-buntansha) FUKUMOTO Seiji  University of Tokuo, Faculty of Medicine, Assistant Professor, 医学部・附属病院(分), 助手 (30202287)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsosteoblast / aging / osteoporosis / matrix proteins / collagen / integrin / adhesion molecules / bone marrow cells / 骨髄間質細胞
Research Abstract

Modulation of TGF-beta actions in osteoblasts by bone matrix proteins
We demonstrated that decorin, a bone matrix protein synthesized by osteoblasts, binds TGF-beta and enhances the binding to its receptors on osteoblastic cells, resulting in the augmentation of bioactivity of TGF-beta. Thus, decorin is not only a component of bone matrix but may be involved in the bone formation that is stimulated by TGF-beta.
Involvement of collagen-integrin interactions in osteoblastic differentiation
Interactions of osteoblastic cells to type I collagen (COL) via alpha2beta1 integrin were shown to be required for osteoblastic differentiation. The binding of COL to the integrin provoked tyrosine phosphorylation and activation of focal adhesion kinase (FAK) and ERK,a member of MAP kinase family. Several inhibitors that inhibit FAK suppressed collagen-induced osteoblastic differentiation. Furthermore, decrease in FAK expression with the stable expression of antisense mRNA for FAK disrupted both ERK activ … More ation and osteoblastic differentiation. Because transient expression of protein phosphatase CL100 that inactivates ERK prevented the differentiation, the direct involvement of ERK was suggested. These observations indicate that cell-matrix interactions, especially COL-integrin interactions, are essentially involved in the osteoblastic differentiation via activations of signaling cascades directly associated with the integrin, FAK and ERK.
Osteoblastic differentiation in bone marrow cells in advancing with age
P6 strain of senescence-accerelated mice (SAM) is a murine model of involutional osteoporosis. We showed that osteoblastogenesis of bone marrow stromal cells was impaired in SAMP6 mice compared with the control SAMR1 mice. Treatment with interleukin (IL)-11 could restore this disturbance. We further showed that IL-11 expression in bone marrow cells of SAMP6 was less than that of SAMR1, suggesting that insufficient IL-11 actions causes the impaired osteoblastogenesis in SAMP6. Thus, a decrease in actions of cytokines like IL-11 is further to be investigated for the pathogenesis of involutional osteoporosis. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Konosuke Nakayama: "Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia." Journal of Clinical Endocrinology and Metabolism. 81・2. 607-611 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seiji Fukumoto: "Absence of mutations in parathyroid hormone (PTH) /PTH-rolated protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type 1b." Journal of Clinical Endocrinology and Metabolism. 81・7. 2554-2558 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshiaki Kodama: "Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-β receptors in rat preosteoblastic RCT-1 cells." Endocrine Journal. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuhiro Takeuchi: "Relationship between actions of transforming growth factor-β and cell surface expression of its receptors in clonal osteoblastic cells." Journal of Cellular Phystology. 162. 315-321 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuhiro Takeuchi: "Differentiation and cell-surface expression of transforming growth factor-β receptors are regulated by interaction with matrix collagen in murine osteoblastic cells." Journal of Biological Chemistry. 271. 3938-3944 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toshio Matsumoto: "Molecular and cellular biology of bone" JAI Press,Zaidi,M. (eds),(in press), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takeuchi, Y.et al.: "Relationship between actions of transforming growth factor-beta and cell surface expression of its receptors in clonal osteoblastic cells." J Cell Physiol.162. 315-321 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takeuchi, Y.et al.: "Differentiation and cell surface expression of transforming growth factor-beta receptors are regulated by interaction with matrix collagen in murine osteoblastic cells." J Biol Chem.271. 3938-3944 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakayama, K.et al.: "Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia." J Clin Endoc Metab. 81. 607-611 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukumoto, S.et al.: "Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type lb." J Clin Endoc Metab. 81. 2554-2558 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kodama, Y.et al.: "Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors in rat preosteoblastic RCT-1 cells." Endocrine J. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsumoto, T.et al.: "Systemic control of bone formation. In : Zaidi, M.(eds) Molecular and cellular biology of bone." JAI Press. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konosuke Nakayama: "Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia." Journal of Clinical Endocrinology and Metabolism. 81・2. 607-611 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seiji Fukumoto: "Absence of mutations in parathyroid hormone(PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type 1b." Journal of Clinical Endocrinology and Metabolism. 81・7. 2554-2558 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshiaki Kodama: "Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-β receptors in rat preosteoblastic RCT-1 cells." Endocrine Journal. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 竹内 靖博: "分子骨代謝学と骨粗鬆症" メディカル・レビュー社 松本俊夫編, 405 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toshio Matsumoto: "Molecular and cellular biology of bone" JAI Press,Zaidi,M.(eds)(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuhiro Takeuchi: "Relationship between actions of transforming growth factor-β and cell surface expression of its receptors in clonal osteoblastic cells" Journal of Cellular Physiology. 162. 315-321 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yasuhiro Takeuchi: "Differentiation and cell-surface expression of transforming growth factor-β receptors are regulated by interaction with matrix collagen in murine osteo blastic cells" Journal of Biological Chemistry. 271. 3938-3944 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Konosuke Nakayama: "Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia" Journal of Clinical Endocrinology and Metabolism. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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