Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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BMP-2-Enhanced Chondrogenesis Involves p38 MAPK-mediated Down-Regulation of Wnt-7a Pathway

  • Jin, Eun-Jung (Department of Biology, College of Natural Sciences, Kyungpook National University) ;
  • Lee, Sun-Young (Department of Biology, College of Natural Sciences, Kyungpook National University) ;
  • Choi, Young-Ae (Department of Biology, College of Natural Sciences, Kyungpook National University) ;
  • Jung, Jae-Chang (Department of Biology, College of Natural Sciences, Kyungpook National University) ;
  • Bang, Ok-Sun (School of Biological Sciences, Seoul National University) ;
  • Kang, Shin-Sung (Department of Biology, College of Natural Sciences, Kyungpook National University)
  • Received : 2006.09.20
  • Accepted : 2006.11.13
  • Published : 2006.12.31
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Abstract

The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates $Wnt-7a/{\beta}$-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of ${\beta}$-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with ${\beta}$-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of ${\beta}$-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of ${\beta}$-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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