BMP-2-Enhanced Chondrogenesis Involves p38 MAPK-mediated Down-Regulation of Wnt-7a Pathway.
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/b-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 b-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with b-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 b-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 b-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells.[1]References
- BMP-2-Enhanced Chondrogenesis Involves p38 MAPK-mediated Down-Regulation of Wnt-7a Pathway. Jin, E.J., Lee, S.Y., Choi, Y.A., Jung, J.C., Bang, O.S., Kang, S.S. Mol. Cells (2006) [Pubmed]
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