Disruption of actin cytoskeleton induces chondrogenesis of mesenchymal cells by activating protein kinase C-alpha signaling

Disruption of actin cytoskeleton with cytochalasin D has been known to indu ce chondrogenic differentiation of chick embryo Limb bud mesenchymal cells. However, the mechanism(s) for the induction of chondrogenesis by cytochala sin D is not yet-clearly known, In the present study, we examined possible involvement of protein kinase C (PKC) and extracellular signal-regulated pr otein kinase (Erk-1) in chondrogenesis of mesenchymal cells induced by disr uption of actin cytoskeleton. Disruption of actin cytoskeleton with cytocha lasin D or latrunculin B induced chondrogenesis of mesenchymal cells cultur ed at subconfluent cell density, as determined by type II collagen expressi on. Among the expressed PKC isoforms, cytochalasin D dramatically increased expression and activation of PKC alpha in a dose-dependent manner, and inh ibition or downregulation of PKC alpha blocked cytochalasin D-induced chond rogenesis. Cytochalasin D also downregulated Erk-1 phosphorylation that is associated with chondrogenesis. Our results, therefore, suggest that disrup tion of actin cytoskeleton induces chondrogenesis of mesenchymal cells by a ctivating PKC alpha and by inhibiting Erk-1 signaling. (C) 2000 Academic Pr ess.