|
KMID : 0578320060220030353
|
|
Molecules and Cells
2006 Volume.22 No. 3 p.353 ~ p.359
|
|
|
BMP-2-Enhanced Chondrogenesis Involves p38 MAPK-mediated Down-Regulation of Wnt-7a Pathway
|
|
Jin Eun-Jung
Lee Sun-Young
Choi Young-Ae
Jung Jae-Chang
Bang Ok-Sun
Kang Shin-Sung
|
|
|
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/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.
|
|
|
KEYWORD
|
|
|
β-Catenin, Chondrogenesis, p38 MAPK, Sox9, Wnt-7a
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|