2000 Fiscal Year Final Research Report Summary
Investigation of roles of cbfa1 in regulation of chondrocyte proliferation and differentiation.
Project/Area Number |
11671839
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional basic dentistry
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Research Institution | Osaka 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)
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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)
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Project Period (FY) |
1999 – 2000
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Keywords | cbfa1 / chondrocyte / maturation / endochondral ossification / skeletogenesis |
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.
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Research Products
(14 results)
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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