Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment

Takayuki Furumatsu, Masanao Tsuda, Noboru Taniguchi, Yoshitaka Tajima, Hiroshi Asahara

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

The transcriptional activation by SRY-type high mobility group box 9 (SOX9) and the transforming growth factor β (TGF-β) signals are necessary for chondrogenic differentiation. We have previously shown that CREB-binding protein (CBP/p300) act as an important SOX9 co-activator during chondrogenesis. In the present study, we investigated the relationship between TGF-β-dependent Smad2/3 signaling pathways and the SOX9-CBP/p300 transcriptional complex at the early stage of chondrogenesis. Overexpressed Smad3 strongly induced the primary chondrogenesis of human mesenchymal stem cells. In addition, Smad3 enhanced the transcriptional activity of SOX9 and the expression of α1(II) collagen gene (COL2A1), and small interference RNA against Smad3 (si-Smad3) inhibited them. We observed that Smad2/3 associated with Sox9 in a TGF-β-dependent manner and formed the transcriptional complexes with SOX9 on the enhancer region of COL2A1. Interestingly, the association between Sox9 and CBP/p300 was increased by Smad3 overexpression and was suppressed by si-Smad3. Our findings indicate that Smad3 has a stronger potential to stimulate the SOX9-dependent transcriptional activity by modulating the interaction between SOX9 and CBP/ p300, rather than Smad2. This study suggests that the Smad3 pathway presents a key role for the SOX9-dependent transcriptional activation in primary chondrogenesis.

Original languageEnglish
Pages (from-to)8343-8350
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number9
DOIs
Publication statusPublished - Mar 4 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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