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.
Jin
Eun-Jung
EJ
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
Lee
Sun-Young
SY
Choi
Young-Ae
YA
Jung
Jae-Chang
JC
Bang
Ok-Sun
OS
Kang
Shin-Sung
SS
D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002642:Chick Embryo; D020219:Chondrogenesis; D015536:Down-Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism; D014921:Wings, Animal / Q000196:embryology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D030161:Avian Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014452:Ubiquitins; C490509:WNT7A protein, Gallus gallus; D051153:Wnt Proteins; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex