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J. Biol. Chem., Vol. 282, Issue 23, 17123-17131, June 8, 2007

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Regulation of Type II Collagen Expression by Histone Deacetylase in Articular Chondrocytes^*

From the Department of Life Sciences, Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea

Histone deacetylase (HDAC) regulates various cellular processes by modulating gene expression. Here, we investigated the role of HDAC in the expression of type II collagen, a marker of differentiated chondrocytes. We found that HDAC activity in primary articular chondrocytes decreases during dedifferentiation induced by serial monolayer culture and that the activity recovered during redifferentiation induced by three-dimensional culture in a cell pellet. Inhibition of HDAC with trichostatin A or PXD101 was sufficient to block type II collagen expression in primary culture chondrocytes. HDAC inhibition also blocked the redifferentiation of dedifferentiated chondrocytes by suppressing the synthesis and accumulation of type II collagen. HDAC inhibition promoted the expression of Wnt-5a, which is known to inhibit type II collagen expression, and knockdown of Wnt-5a blocked the ability of HDAC inhibitors to suppress type II collagen expression. In addition, the induction of Wnt-5a expression by HDAC inhibitors was associated with acetylation of the Wnt-5a promoter. Taken together, our results suggest that HDAC promotes type II collagen expression by suppressing the transcription of Wnt-5a.

Received for publication, January 22, 2007 , and in revised form, March 19, 2007.

^* This work was supported by grants from the Korea Research Foundation (KRF-2005-201-C00034) and the Korea Science and Engineering Foundation (R01-2005-000-10307-0) and from the Korean Ministry of Health and Welfare (A06-0282-AA1018-06N1-00010A). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Life Sciences, Gwangju Institute of Science and Technology, Buk-Gu, Gwangju 500-712, Korea. Tel.: 82-62-970-2497; Fax: 82-62-970-2484; E-mail: jschun{at}gist.ac.kr.

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