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Investigation of roles of cbfa1 in regulation of chondrocyte proliferation and differentiation.

Research Project

Project/Area Number 11671839
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ENOMOTO-IWAMOTO Motomi  Graduate School of Dentistry, Osaka University, Assistant Professor, 大学院・歯学研究科, 講師 (80203644)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Masahiro  Graduate School of Dentistry, Osaka University, Assistant Professor, 大学院・歯学研究科, 講師 (30223431)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordscbfa1 / chondrocyte / maturation / endochondral ossification / skeletogenesis / Cbfa1 / OSF2
Research Abstract

We investigated the role of cbfa1, a transcription factor of runt family, in regulation of chondrocyte proliferation and differentiation in the process of endochondral ossification. The results obtained in this research are as follows :
1. Cbfa1 is expressed in hypertrophic zone of growth plate cartilage.
2. Forced expression of cbfa1 stimulated maturation and calcification in chondrocytes in vitro.
3. Forced expression of a dominant negative form of cbfa1 lacking the C-terminal transactivation domain (dn-cbfa1) completely inhibited maturation and calcification in chondrocytes in vitro.
4. Forced expression of cbfa1 in the developing chick limb bud induced precocious endochondral ossification and joint fusion.
5. BMPs did not upregulate cbfa1 gene expression.
6. The effects of dn-cbfa1 on chondrocyte maturation was partially rescued by the addition of BMP2.
7. The transgenic mice that over-expressed cbfa1 and dn-cbfa1 in chondrocytes displayed dwarfism ; cbfa1 induced precocious and ectopic endochodnral ossification, while dn-cbfa1 strongly suppressed endochondral ossification.
These results indicate that expression of cbfa1 in chodrocytes is essential for progression of endochondral ossification.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Enomoto,H. et al: "Cbfa1 is a positive regulatory factor in chondrocyte maturation."J.Biol.Chem.. 275. 8695-8702 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwamoto,M. et al: "Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development."J.Cell.Biol.. 150. 27-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ueta,C. et al: "Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes."J.Cell Biol.. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto,M. et al: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation."J.Bone Miner.Res.. 15. 1695-1688 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 岩本資己 et al: "軟骨の発生と再生"実験医学. 18. 1325-1332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto et al: "Participation of cbfa1 in regulation of chondrocyte differentiation."Osteoarthritis Catilage.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 岩本資己 et al: "新・分子骨代謝学と骨粗鬆症"メディカル・ビュー社(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto, H., Enomoto-Iwamoto, M., Iwamoto, M., Takemoto, S., Himeno, M., Nomura, S., Kitamura, Y., Kishimoto, T., Komori, T.: "Cbfa-1 is a positive regulatory factor in chondrocyte maturation."J.Biol.Chem.. 275. 8695-8702 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwamoto M, Higuchi Y, Koyama E, Enomoto-Iwamoto M, Kurisu K, Yeh H, Abrams WR, Rosenbloom J, Pacifici M: "Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development."J Cell Biol. 150. 27-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ueta, C., Iwamoto, M., Kanatani, N., Yoshiada, C., Liu, Yang, Enomoto-Iwamoto, M., Ohmori, T., Enomoto, H., Nakata, K., Takada, K., Kurisu, K.and Komori, T.: "Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes."J.Cell Biol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto M, Nakamura T, Alkawa T, Higuchi Y, Yuasa T, Yamaguchi A, Nohno T, Noji S, Matsuya T, Kurisa K, Koyama E, Pacifici M, Iwamoto M: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation."J Bone Miner Res. 15. 1659-1668 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., Iwamoto M.: "Development and regeneration of cartilage. (in Japanese)"Experimental Medicine. 18. 1325-1332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., Enomoto, Y., Komori, T., and Iwamoto, M.: "Participation of cbfa1 in regulation of chondrocyte differentiation."Osteoarthritis & Cartilage. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., Koyama, E., Nohno, T.: "Limb morphogenesis and its regulation factors. In New bone molecular metabolism and osteoporosis (ed.by Matsumoto, T.) Medical (in Japanese)"View Press Co.Tokyo (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Enomoto,H. et al: "Cbfa1 is a positive regulatory factor in chondrocyte maturation."J.Biol.Chem.. 275. 8695-8702 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwamoto,M. et al: "Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development."J.Cell Biol.. 150. 27-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueta,C. et al: "Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes."J.Cell Biol.. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto-Iwamoto,M. et al: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation"J.Bone Miner.Res.. 15. 1695-1688 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩本資己 et al: "軟骨の発生と再生"実験医学. 18. 1325-1332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩本資己 et al: "新・分子骨代謝学と骨粗鬆症"メディカル・ビュー社(印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Jikko: "The role of hepatocyte growth factor in growth plate cartilage"J. Bone Miner. Metab.. 16. 170-177 (1999)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Iwamoto: "Actions of Hedgehog Proteins on sheletal cells"Crit. Rev. Oral. Biol. Med.,. 10. 477-486 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Enomoto H.: "Cbfa-1 is a positive regulatory factor in chondrocyte maturation"J. Biol. Chem. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 岩本資己: "軟骨の発生と再生"実験医学 (印刷中). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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