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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)
Publication Information
Molecules and Cells / v.22, no.3, 2006 , pp. 353-359 More about this Journal
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
${\beta}$-Catenin; Chondrogenesis; p38 MAPK; Sox9; Wnt-7a.;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 32  (Related Records In Web of Science)
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