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Cited by 587

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog

Open access
Yoshida, Carolina A., Yamamoto, Hiromitsu, Fujita, Takashi, Furuichi, Tatsuya, Ito, Kosei, Inoue, Ken-ichi, Yamana, Kei, Zanma, Akira, Takada, Kenji, Ito, Yoshiaki, Komori, Toshihisa·2004·Genes & Development

Abstract

The differentiation of mesenchymal cells into chondrocytes and chondrocyte proliferation and maturation are fundamental steps in skeletal development. Runx2 is essential for osteoblast differentiation and is involved in chondrocyte maturation. Although chondrocyte maturation is delayed in Runx2 -deficient ( Runx2 –/– ) mice, terminal differentiation of chondrocytes does occur, indicating that additional factors are involved in chondrocyte maturation. We investigated the involvement of Runx3 in chondrocyte differentiation by generating Runx2 -and- Runx3 -deficient ( Runx2 –/– 3 –/– ) mice. We found that chondrocyte differentiation was inhibited depending on the dosages of Runx2 and Runx3 , and Runx2 –/– 3 –/– mice showed a complete absence of chondrocyte maturation. Further, the length of the limbs was reduced depending on the dosages of Runx2 and Runx3 , due to reduced and disorganized chondrocyte proliferation and reduced cell size in the diaphyses. Runx2 –/– 3 –/– mice did not express Ihh, which regulates chondrocyte proliferation and maturation. Adenoviral introduction of Runx2 in Runx2 –/– chondrocyte cultures strongly induced Ihh expression. Moreover, Runx2 directly bound to the promoter region of the Ihh gene and strongly induced expression of the reporter gene driven by the Ihh promoter. These findings demonstrate that Runx2 and Runx3 are essential for chondrocyte maturation and that Runx2 regulates limb growth by organizing chondrocyte maturation and proliferation through the induction of Ihh expression.

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Metadata

Authors
Yoshida, C. A., Yamamoto, H., Fujita, T., Furuichi, T., Ito, K., Inoue, K.-I., Yamana, K., Zanma, A., Takada, K., Ito, Y., & Komori, T.
Venue
Genes & Development
Published
2004-04-15
Volume
18
Issue
8
Pages
952-963
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2122433264
Cited by
587
References
34
Type
posted content
Language
en
Open access
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Yoshida, C. A., Yamamoto, H., Fujita, T., Furuichi, T., Ito, K., Inoue, K.-I., Yamana, K., Zanma, A., Takada, K., Ito, Y., & Komori, T. (2004). Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes & Development. https://doi.org/10.1101/gad.1174704

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