BMP-2 treatment of C3H10T1/2 mesenchymal cells blocks MMP-9 activity during chondrocyte commitment.
Members of both the Wnt and bone morphogenetic protein (BMP) families of signaling molecules have been implicated in the regulation of cartilage development. We explored the underlying mechanism of BMP-2-induced chondrocyte commitment of C3H10T1/2 cells. Treating cells with exogenous BMP-2 was tied to chondrocyte commitment by inhibiting matrix metalloproteinase-9 activity (MMP-9: 92 kDa type IV collagenase/gelatinase B). Glycogen synthase kinase (GSK)-3beta inhibition by its specific inhibitor blocked BMP-2-induced chondrocyte commitment by stimulating MMP-9 activity. These findings indicate that the downregulation of MMP-9 by BMP-2 is associated with chondrocyte commitment, and that the GSK-3beta signaling pathway is involved in this process.
Choi
Young-Ae
YA
Department of Biological Sciences, College of Natural Sciences, Kyungbook National University, Daegu 702-701, South Korea.
Kang
Shin-Sung
SS
Jin
Eun-Jung
EJ
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000201:enzymology; D015398:Signal Transduction
D055396:Bone Morphogenetic Protein 2; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D020780:Matrix Metalloproteinase 9