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Originally published In Press as doi:10.1074/jbc.M206771200 on October 15, 2002

J. Biol. Chem., Vol. 277, Issue 51, 50112-50120, December 20, 2002
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Basic Helix-loop-helix Protein DEC1 Promotes Chondrocyte Differentiation at the Early and Terminal Stages*

Ming ShenDagger , Eri YoshidaDagger , Weiqun Yan§, Takeshi Kawamoto, Ketut Suardita, Yasuhiko Koyano, Katsumi Fujimoto, Mitsuhide Noshiro, and Yukio Kato||

From the Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan, the § Institute for Frontier Medical Sciences, Jilin University, Changchun 130021, China, and the  Department of Orthopeadics Surgery, Jikei University School of Medicine, Minato, Tokyo 105, Japan

The mRNA level of basic helix-loop-helix transcription factor DEC1 (BHLHB2)/Stra13/Sharp2 was up-regulated during chondrocyte differentiation in cultures of ATDC5 cells and growth plate chondrocytes, and in growth plate cartilage in vivo. Forced expression of DEC1 in ATDC5 cells induced chondrogenic differentiation, and insulin increased this effect of DEC1 overexpression. Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) suppressed DEC1 expression and the differentiation of ATDC5 cells, but DEC1 overexpression antagonized this inhibitory action of PTH/PTHrP. Transforming growth factor-beta or bone morphogenetic protein-2, as well as insulin, induced DEC1 expression in ATDC5 cultures where it induced chondrogenic differentiation. In pellet cultures of bone marrow mesenchymal stem cells exposed to transforming growth factor-beta and insulin, DEC1 was induced at the earliest stage of chondrocyte differentiation and also at the hypertrophic stage. Overexpression of DEC1 in the mesenchymal cells induced the mRNA expressions of type II collagen, Indian hedgehog, and Runx2, as well as cartilage matrix accumulation; overexpression of DEC1 in growth plate chondrocytes at the prehypertrophic stage increased the mRNA levels of Indian hedgehog, Runx2, and type X collagen, and also increased alkaline phosphatase activity and mineralization. To our knowledge, DEC1 is the first transcription factor that can promote both chondrogenic differentiation and terminal differentiation.

* This work was supported by a grant-in-aid for science from the Ministry of Education, Science, Sports and Culture of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Both authors contributed equally to this study.

|| To whom correspondence should be addressed. Fax: 81-82-257-5629; E-mail: ykato@hiroshima-u.ac.jp.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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