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

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121 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2414-2419
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number7
DOIs
Publication statusPublished - Feb 15 2005
Externally publishedYes

Keywords

  • Cartilage
  • Coactivator 1α
  • Limb development
  • Mesenchymal stem cell
  • Peroxisome proliferator-activated receptor γ

ASJC Scopus subject areas

  • General

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  • Cite this

    Kawakami, Y., Tsuda, M., Takahashi, S., Taniguchi, N., Esteban, C. R., Zemmyo, M., Furumatsu, T., Lotz, M., Belmonte, J. C. I., & Asahara, H. (2005). Transcriptional coactivator PGC-1α regulates chondrogenesis via association with Sox9. Proceedings of the National Academy of Sciences of the United States of America, 102(7), 2414-2419. https://doi.org/10.1073/pnas.0407510102