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Development of a therapeutic method of bone repair using BMP responding mesencbymal cells

Research Project

Project/Area Number 09557140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Morphological basic dentistry
Research InstitutionShowa University

Principal Investigator

YAMAGUCHI Akira  School of Dentistry, Showa University, Associate Professor, 歯学部, 助教授 (00142430)

Co-Investigator(Kenkyū-buntansha) KATAOKA Hiroko  School of Dentistry, Showa University, Assistant, 歯学部, 助手 (60286846)
KOBAYASHI Makoto  School of Dentistry, Showa University, Lecturer, 歯学部, 講師 (80186767)
OHNO Kousuke  School of Dentistry, Showa University, Associate Professor, 歯学部, 助教授 (30112725)
SAKAMOTO Keizou  School of Medicine, Showa University, Professor, 歯学部, 教授 (50119195)
池田 通  昭和大学, 歯学部, 講師 (00211029)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsBone regeneration / BMP / Bone Formation / osteoblast / 骨 / 再生
Research Abstract

In 1971, Urist gave name bone morphogenetic protein (BMP) for the protein which was extracted from demineralized bone matrix with bloactivity inducing ectopic bone formation. This indicates that osteoprogenitor cells, which can differentiate into osteoblasts in response to BMP, are present in muscle and subcutaneous tissue. Human BMP cDNAs were first cloned in 1988, and over 15 cDNAs encoding BMPs have been cloned at present. Recently BMP receptors have also cloned. We have investigated the role of BMP-2 in regulation of differentiation of skeletal mesenchymal cells. In the present study, we conducted several experiments to develop a novel therapeutic method of bone repair, and obtained the following results.
1) We confirmed the expression of BMP receptors (IA, IB and II) in primary rat osteoblastic cells by in situ hybridization and immunohistochemistry.
2) We investigated the effect of BMP-2 on osteoblast differentiation using various culture cells, and demonstrated that the effects of BMP-2 varied among cell types used.
3) We demonstarted that BMP-2 induced osteoblast differentiation in human muscles and skin fibroblasts.
4) We transplanted BMP-2IPGS complex with osteoprogenitor cells into bone defects. This method generated new bone more effectively than that simply transplanted BMP-2IPGS.
5) We triad to make antibodies against BMP receptor IA, but could not obtain neutralizing antibodies.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kusafuka K, Yamaguchi A, et al.: "Expression of bone morphogenetic proteins in salivary pleomorphic adenomas." Virchows Archiv.432. 247-253 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wada Y, Yamaguchi A, et al.: "Changes in osteoblast phenotype during differentiation of enzymatically isolated rat calvaria cells." BONE. 224. 479-485 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawasaki K, Yamaguchi A, et al.: "Effcets of recombinant human BMP-2 on differentiation of cells isolated from human bone, muscle and skin." BONE. 223. 223-231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gao Y-H, Yamaguchi A, et al.: "Potential role of Cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis : regulation of mRNA expression of osteoclast differentiation factor (ODF)." Biochem. Biophys. Res.Commun.252. 607-702 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harada H, Yamaguchi A, et al.: "Cbfa1 isoforms exert functional differences in osteoblast differentiation." J.Biol.Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi M, Yamaguchi A, et al.: "Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament." J.Dent.Res.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kusafuka K,Yamaguchi A,Kayano T,Fujiwara M,and Takemura T.: "Expression of bone morphogenetic proteins in salivary pleomorphic adenomas." Virchows Archiv. 432. 247-253 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wada Y,Kataoka H,Yokose S,Ishizuya T,Miyazono K,Gao Yu-Hao, Shibasaki Y,and Yamaguchi A.: "Changes in osteoblast phenotype during differentiation of enzymatically isolated rat calvaria cells." Bone. 22. 479-485 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawasaki K,Aihara M,Honmo J,Sakurai S,Yamaguchi A,Wozney JM,Sakamoto K,and Fujimaki E: "Effects of recombinant human BMP-2 on differentiation of cells isolated from human bone, muscle and skin." Bone. 23. 223-231 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gao Y-H,Shinki T,Yuasa T,Kataoka-Enomoto H,Komori T,Suda T and Yamaguchi A: "Potential role of Cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis : regulation of mRNA expression of osteoclast differentiation factor (ODF)." Biochem.Biophys.Res.Commun.252. 697-702 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harada H,Tagashira S,Fujiwara M,Ogawa S,Katsumata T,Yamaguchi A,Komori T,and Nakatsuka M: "Cbfa1 isoforms exert functional differences in osteoblast differentiation." J Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi M,Takiguchi T,Suzuki R,Yamaguchi A,Deguchi K,Shionome M,Miyazawa Y,Nishihara T,Nagumo M,and Kasegawa K: "Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament." J.Dent.Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kusafuka K,Yamaguchi A,et al.: "Expression of bone morphogenetic proteins in salivary pleomorphic adenomas." Virchows Archiv.432. 247-253 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wada Y,Yamaguchi A,et al.: "Changes in osteoblast phenotype during differentiation of enzymatically isolated rat calvaria cells." BONE. 224. 479-485 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawasaki K,Yamaguchi A,et al.: "Effects of recombinant human BMP-2 on differentiation of cells isolated from human bone,muscle and skin." BONE. 223. 223-231 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Gao Y-H,Yamaguchi A,et al.: "Potential role of Cbfa1,an essential transcriptional factor for osteoblast differentiation,in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor(ODF)." Biochem.Biophys.Res.Commun.252. 607-702 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Harada H,Yamaguchi A,et al.: "Cbfa1 isoforms exert functional differences in osteoblast differentiation." J.Biol.Chem.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi M,Yamaguchi A,et al.: "Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament." J.Dent.Res.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Komori T, Yagi H, Yamaguchi A, et al.: "Targeted disruption of Cbfa1 results in complete lack bone formation owing to the maturation arrest of osteoblasts." Cell. 89. 755-764 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishizuya T, Yokose S, Yamaguchi A, et al: "Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteobllastic cells." J.Clin.Invest.99. 2961-2970 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawasaki K, Gao Y, Yamaguchi A, et al.: "Osteoclasts are present in gp 130-deficient mice." Endocrinology. 138. 4959-4965 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura T, Aikawa T, Yamaguchi A, et al.: "Hedgehogs synergiatically promote osteoblast differentiation with BMP-2." Biochem.Biophys.Res.Commun.237. 465-469 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishida S, Nakamura T, Yamaguchi A, et al.: "The effect of monoclonal anti-human GP130 antibody on the bone metabolism in normal and ovariectomized rats." Calcif Tissue Int. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Wada Y, Kataoka H, Yamaguchi A, et al.: "Changes in osteoblast phenotype during differentiation of enzymatically isolated rat calvaria cells." BONE. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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