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Research of the signals of osteoblast differentiation and mineralization including menin and Smad

Research Project

Project/Area Number 15590977
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKobe University

Principal Investigator

KAJI Hirohi  Kobe University, Graduate School of Medicine, 大学院・医学系研究科, 助手 (90346255)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Toshitsugu  Shimane University, Faculty of Medicine, 医学部, 教授 (00226458)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsTGF-beta / Menin / Smad / osteoblast / JunD / bone formation / glucocorticoid / parathyroid hormone / 分化 / TGFβ / Smad3 / アポトーシス
Research Abstract

We previously revealed that menin, a product of multiple endocrine neoplasia type I gene, is required for the early differentiation of osteoblast and inhibits it at later stage. Moreover, we proposed that Smad3, TGF-beta-specific signaling molecule, is important for bone formation. On the other hand, parathyroid hormone (PTH) is one of most potent bone formation stimulating agents. However, the mechanism, by which PTH stimulates bone formation, remains unknown. In the present study, we demonstrated that PTH-Smad3 axis exerts anti-apoptotic effects in osteoblasts and might be involved in the bone anabolic action of PTH. In addition, dexamethasone, a glucocorticoid analogue, inhibits alkaline phosphatase activity and type I collagen expression, presumably by suppressing Smad3-induced transcriptional activity but not by modulating Smad3 expression in osteoblasts. This evidence might be partially related to the inhibitory action of glucocorticoid on osteoblastic bone formation. On the other hand, we demonstrated that menin interacts physically and functionally with Runx2 as well as Smad 1/5 in uncommited mesenchymal stem cells, but not in well differentiated osteoblasts. In osteoblasts, the interaction of menin and TGF-beta/Smad3 pathway negatively regulates the BMP-2/Smad1/5- and Runx2-induced transcriptional activities leading to inhibition of late stage differentiation. Moreover, menin suppresses osteoblast maturation, in part, by inhibiting the differentiation actions of JunD, AP-1 factor.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 2003 Other

All Journal Article (11 results) Publications (1 results)

  • [Journal Article] Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD2005

    • Author(s)
      内藤 純子
    • Journal Title

      Journal of Biological Chemstry 280.6

      Pages: 4785-4791

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dexamethasone suppresses Smad3 pathway in osteoblastic cells2005

    • Author(s)
      余 美慧
    • Journal Title

      Journal of Endocrinology 185.1

      Pages: 131-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD.2005

    • Author(s)
      Junko, Naito
    • Journal Title

      Journal of Biological Chemistry 280-6

      Pages: 4785-4791

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dexamethasone suppresses Smad3 pathway in osteoblastic cells.2005

    • Author(s)
      Mei-Fway, Iu
    • Journal Title

      Journal of Endocrinology 185-1

      Pages: 131-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD.2005

    • Author(s)
      内藤純子
    • Journal Title

      Journal of Biological Chemistry 280.6

      Pages: 4785-4791

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dexamethasone suppresses Smad3 pathway is osteoblastic cells.2005

    • Author(s)
      余美慧
    • Journal Title

      Journal of Endocrinology (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx22004

    • Author(s)
      宗和 秀明
    • Journal Title

      Journal of Biological Chemstry 279・39

      Pages: 40267-40275

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2.2004

    • Author(s)
      Hideaki, Sowa
    • Journal Title

      Journal of Biological Chemistry 279-39

      Pages: 40267-40275

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2.2004

    • Author(s)
      宗和秀明
    • Journal Title

      Journal of Biological Chemistry 279・39

      Pages: 40267-40275

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Parathyroid hormone-Smad3 axis exerts anti-apoptotic action and augments anabolic action of transforming growth factor β in osteoblasts2003

    • Author(s)
      宗和 秀明
    • Journal Title

      Journal of Biological Chemstry 278・52

      Pages: 52240-52252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Parathyrooid hormone-Smad3 axis exerts anti-apoptotic action and augments anabolic action of transforming growth factor β in osteoblasts.2003

    • Author(s)
      Hideaki, Sowa
    • Journal Title

      Journal of Biological Chemistry 278-52

      Pages: 52240-52252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 宗和秀明: "Parathyrooid hormone-Smad3 axis exerts anti-apoptotic action and augments anabolic action of transforming growth factor β in osteoblasts"Journal of Biological Chemstry. 278・52. 52240-52252 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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