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Transcriptional Coactivator PGC-1α Regulates Chondrogenesis via Association with Sox9

Yasuhiko Kawakami, Masanao Tsuda, Shigeru Takahashi, Noboru Taniguchi, Concepción Rodríguez Esteban, Michihisa Zemmyo, Takayuki Furumatsu, Martin Lotz, Juan Carlos Izpisúa Belmonte, Hiroshi Asahara and Bruce M. Spiegelman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 7 (Feb. 15, 2005), pp. 2414-2419
Stable URL: http://www.jstor.org/stable/3374629
Page Count: 6
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Transcriptional Coactivator PGC-1α Regulates Chondrogenesis via Association with Sox9
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Abstract

Chondrogenesis is a multistep pathway in which multipotential mesenchymal stem cells (MSC) differentiate into chondrocytes. The transcription factor Sox9 (SRY-related high mobility group-Box gene 9) regulates chondrocyte differentiation and cartilage-specific expression of genes, such as Col2a1 (collagen type II α1). However, Sox9 expression is detected not only in chondrogenic tissue but also in nonchondrogenic tissues, suggesting the existence of a molecular partner(s) required for Sox9 to control chondrogenesis and chondrogenic gene expression. Here, we report identification of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) as a coactivator for Sox9 during chondrogenesis. Expression of PGC-1α is induced at chondrogenesis sites during mouse embryonic limb development and during chondrogenesis in human MSC cultures. PGC-1α directly interacts with Sox9 and promotes Sox9-dependent transcriptional activity, suggesting that PGC-1α acts as a transcriptional coactivator for Sox9. Consistent with this finding, PGC-1α disruption in MSC by small interfering RNA inhibits Col2a1 expression during chondrogenesis. Furthermore, overexpression of both PGC-1α and Sox9 induced expression of chondrogenic genes, including Col2a1, followed by chondrogenesis in the MSC and developing chick limb. Together, our results suggest a transcriptional mechanism for chondrogenesis that is coordinated by PGC-1α.

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