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2005 Fiscal Year Final Research Report Summary

Enhancement of BMP activity in vivo by heparin and analysis of its molecular mechanisms.

Research Project

Project/Area Number 16591866
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

KAMIJO Ryutaro  Showa University, School of Dentistry, Professor, 歯学部, 教授 (70233939)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Takenobu  Saitama Medical School, School of Medicine, Associate Professor, 医学部, 助教授 (80245802)
MIYAMOTO Yoichi  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (20295132)
TAKAMI Masamichi  Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (80307058)
Project Period (FY) 2004 – 2005
Keywordsheparin / BMP / ectopic bone formation / noggin / samd1 / 5 / 8 / phosphorylation / C2C12 cells
Research Abstract

Although bone morphogenetic proteins (BMPs) are clinically useful for bone regeneration, large amounts of them are required to induce new bone formation in monkeys and humans. We recently found that heparin stimulated BMP activity in vitro. In the present study, we examined whether heparin can enhance the bone formation induced by BMPs in vivo and attempted to determine the molecular mechanisms by which heparin stimulates BMP activity using C2C12 myoblasts. Heparin enhanced BMP-2-induced gene expression and Smad1/5/8 phosphorylation at 24 hours and thereafter, though not within 12 hours. Heparitinase treatment did not affect the response of cells to BMP-2. The half-life of BMP-2 in culture media was prolonged more that 10-fold in the presence of heparin. Although noggin mRNA was induced by BMP-2 within 1 hour regardless of the presence of heparin, noggin failed to inhibit BMP-2 activity in the presence of heparin. Furthermore, simultaneous administration of BMP-2 and heparin in vivo dose-dependently induced larger amounts of mineralized bone tissue than BMP-2 alone. These findings clearly indicate that heparin enhances BMP-induced osteoblast differentiation not only in vitro but also in vivo. They also suggest that heparin protects BMPs from the inhibitory microenvironment around target cells.

  • Research Products

    (11 results)

All 2006 2005 2004

All Journal Article (11 results)

  • [Journal Article] Enhancement of bone formation induced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.2006

    • Author(s)
      Suzuki, O.
    • Journal Title

      Biomaterials 27・13

      Pages: 2671-2681

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhancement of bone formation induced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.2006

    • Author(s)
      Suzuki, O.
    • Journal Title

      biomaterials 27(13)

      Pages: 2671-2681

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE expression in osteoblasts : possible involvement of ERK and p38 MAPKpathways.2005

    • Author(s)
      Takami, M.
    • Journal Title

      FEBS Lett. 579・3

      Pages: 832-838

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.2005

    • Author(s)
      Yasuhara, R.
    • Journal Title

      Biochem. Journal 389・2

      Pages: 315-323

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation and monitoring of cells using a biochip for regenerative medicine.2005

    • Author(s)
      Arai, F.
    • Journal Title

      Transaction of the Japanese Society of Mechanical Engineers 71・711

      Pages: 3239-3245

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IL-1誘導性の軟骨細胞死における一酸化窒素の役割2005

    • Author(s)
      安原 理佳
    • Journal Title

      口腔組織培養学会誌 14・1

      Pages: 55-56

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 破骨細胞分化の初期段階における細胞の形質的特徴の解析2005

    • Author(s)
      望月 文子
    • Journal Title

      口腔組織培養学会誌 14・1

      Pages: 45-46

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE expression in osteoblasts : possible involvement of ERK and p38 MAPK pathways.2005

    • Author(s)
      Takami, M.
    • Journal Title

      FEBS Lett. 579(3)

      Pages: 832-838

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.2005

    • Author(s)
      Yasuhara, R.
    • Journal Title

      Biochem.Journal 389(2)

      Pages: 315-323

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differentiation and monitoring of cells using a biochip for regenerative medicine.2005

    • Author(s)
      Arai, F.
    • Journal Title

      Transaction of the Japanese Society of Mechanical Engineers 71(711)

      Pages: 3239-3245

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biological Mechanisms of Tooth Movement and Craniofacial Adaptation.2004

    • Author(s)
      Takada, T.
    • Journal Title

      Harvard Society for the Advancement of Orthodontics

      Pages: 391

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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