BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway

Mol Cells. 2006 Dec 31;22(3):353-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / metabolism*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism*
  • Chick Embryo
  • Chondrogenesis*
  • Down-Regulation*
  • High Mobility Group Proteins / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • SOX9 Transcription Factor
  • Transcription Factors / metabolism
  • Transfection
  • Transforming Growth Factor beta / metabolism*
  • Ubiquitins / metabolism
  • Wings, Animal / embryology
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Avian Proteins
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • High Mobility Group Proteins
  • Proto-Oncogene Proteins
  • SOX9 Transcription Factor
  • Transcription Factors
  • Transforming Growth Factor beta
  • Ubiquitins
  • WNT7A protein, Gallus gallus
  • Wnt Proteins
  • beta Catenin
  • p38 Mitogen-Activated Protein Kinases
  • Proteasome Endopeptidase Complex