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1999 Fiscal Year Final Research Report Summary

Application of Hedgehog Proteins as Drugs for Induction of Hard Tissues and Repair of Hard Tissue Defects.

Research Project

Project/Area Number 09557145
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

IWAMOTO-ENOMOTO Motomi  Faculty of Dentistry, Osaka University, Assistant Professor, 歯学部, 講師 (80203644)

Co-Investigator(Kenkyū-buntansha) HIGUCHI Yoshinobu  Chugai Pharmaceutical Company, Researcher, 研究員
YAMAGUCHI Akira  School of Dentistry, Nagasaki University, Professor, 歯学部, 教授 (00142430)
IWAMOTO Masahiro  Faculty of Dentistry, Osaka University, Assistant Professor, 歯学部, 講師 (30223431)
Project Period (FY) 1997 – 1999
KeywordsHedgehog / Chondrogenic cells / Osteogenic cells / BMP / Hard tissue repair
Research Abstract

Recent studies have shown that members of the hedgehog protein family have roles in regulating skeletogenesis in the limb and other sites. A member of the family, Sonic hedgehog (Shh) is indicated to be a morphogenetic molecule regulating patterning along the antero-posterior axis of the limb. Another member of the hedgehog family, Indian hedgehog (Ihh), is suggested to serve as an inhibitor of chondrocyte maturation, acting indirectly by inducing PTHrP. We found that implantation of Shh-expressing fibroblasts in nude mice induces ectopic bone formation. The results raised the possibility that skeletal cells may be responsive to hedgehog protein action. In the present study, we investigated this possibility and further pursuited whether hedgehog proteins may be utilized as drugs for repair of hard tissue defects. We obtained the following results;
1.Shh and Ihh acted on osteogenic and chondrogenic cells and stimulated their differentiation.
2.Co-exposure of Shh (or Ihh) and BMP2 synergistically stimulated osteogenic and chondrogenic diferentiation.
3.Recombinant proteins of the amino-terminal portion of Shh strongly enhanced the ability of bone morphogenetic protein-2 (BMP2) to induce ectopic endochondral ossification, when applied intramuscularly in the inguial region in nude mice.
These findings suggest that hedgehog proteins may be used as drugs for repair of hard tissue defects.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] N. Kinto: "Fibroblasts expression Sonic hedgehog induce osteoblast differentiation and ectopic bone formation"FEBS Lett.. 404. 319-323 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Enomoto-Iwamoto: "Involvement of a5b1 integrin in matrix interactions and prolifelation of chondrocytes"J. Bone. Miner. Res.. 12. 1124-1132 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Nakamura: "Induction of osteogenic differentiation by hedgehog proteins"Biochem. Biophys. Res. Commun.. 237. 465-469 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Enomoto-Iwamoto: "Bone Morphogenetic Protein Signaling Is Required for Maintenance of Differentiated Phenotype, Control of Proliferation and Hypertrophy in"J. Cell Biol.. 140. 409-418 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A. Jikko: "The role of hepatocyte growth factor in growth plate cartilage"J. Bone. Miner. Metab.. 16. 170-177 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Imanaka-Yoshida: "Vinculin, talin, integrin a6b1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix"Cell Motil Cytoskel. 42. 1-11 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yagami. K.: "Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb"J. Cell Biol.. 147. 1097-1108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Iwamoto: "Actions of Hedgehog Proteins on skeletal cells"Crit. Rev. Oral. Biol. Med.. 10. 477-486 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩本容泰: "軟骨形成におけるヘッジホッグの役割"ホルモンと臨床. 46. 193-199 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩本容泰: "肢芽形態形成におけるアポトーシス"THE BONE. 13. 89-93 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N. Kinto: "Fibroblasts expression Sonic hedgehog induce osteoblast differentiation and ectopic bone formation."FEBS Lett.. 404. 319-323 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Enomoto-Iwamoto: "Involvement of α5β1 integrin in matrix interactions and proliferation of chondrocytes."J. Bone Miner. Res.. 12. 1124-1132 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Nakamura: "Induction of osteogenic differentiation by hedgehog proteins."Biochem. Biophys. Res. Commun.. 237. 465-469 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Enomoto-Iwamoto: "Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation and hypertrophy in chondrocytes."J. Cell Biol.. 140. 409-418 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Jikko: "The role of hepatocyte growth factor in growth plate cartilage."J. Bone Miner. Metab.. 16. 170-177 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Imanaka-Yoshida: "Vinculin, talin, integrin a6b1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix."Cell Motil Cytoskel.. 42. 1-11 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagami, K.: "Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb."J. Cell Biol.. 147. 1097-1108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Enomoto, H.: "Cbfa-1 is a positive regulatory factor in chondrocyte maturation."J. Biol. Chem.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Iwamoto: "Actions of Hedgehog Proteins on skeletal cells."Crit. Rev. Oral. Biol. Med.. 10. 477-486 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Iwamoto: "The role of hedgehog in cartilage formation. (in Japanese)"Hormone and Clinic. 46. 193-199 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Iwamoto: "Apoptosis in limb morphogenesis."THE BONE. 13. 89-93 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Enomoto-Iwamoto: "Development and regeneration of cartilage. (in Japaneses)"JIKKEN IGAKU. (in press).

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

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Published: 2001-10-23  

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