Lim Y B, Kang S S, Park T K, Lee Y S, Chun J S, Sonn J K
Department of Biology, Teacher's College, Taegu, 702-701, Korea.
Biochem Biophys Res Commun. 2000 Jul 5;273(2):609-13. doi: 10.1006/bbrc.2000.2987.
Disruption of actin cytoskeleton with cytochalasin D has been known to induce chondrogenic differentiation of chick embryo limb bud mesenchymal cells. However, the mechanism(s) for the induction of chondrogenesis by cytochalasin D is not yet clearly known. In the present study, we examined possible involvement of protein kinase C (PKC) and extracellular signal-regulated protein kinase (Erk-1) in chondrogenesis of mesenchymal cells induced by disruption of actin cytoskeleton. Disruption of actin cytoskeleton with cytochalasin D or latrunculin B induced chondrogenesis of mesenchymal cells cultured at subconfluent cell density, as determined by type II collagen expression. Among the expressed PKC isoforms, cytochalasin D dramatically increased expression and activation of PKCalpha in a dose-dependent manner, and inhibition or downregulation of PKCalpha blocked cytochalasin D-induced chondrogenesis. Cytochalasin D also downregulated Erk-1 phosphorylation that is associated with chondrogenesis. Our results, therefore, suggest that disruption of actin cytoskeleton induces chondrogenesis of mesenchymal cells by activating PKCalpha and by inhibiting Erk-1 signaling.
已知用细胞松弛素D破坏肌动蛋白细胞骨架可诱导鸡胚肢芽间充质细胞发生软骨形成分化。然而，细胞松弛素D诱导软骨形成的机制尚不清楚。在本研究中，我们检测了蛋白激酶C（PKC）和细胞外信号调节蛋白激酶（Erk-1）是否可能参与了由肌动蛋白细胞骨架破坏诱导的间充质细胞软骨形成过程。用细胞松弛素D或拉春库林B破坏肌动蛋白细胞骨架可诱导以亚汇合细胞密度培养的间充质细胞发生软骨形成，这通过II型胶原蛋白表达得以确定。在表达的PKC同工型中，细胞松弛素D以剂量依赖性方式显著增加PKCalpha的表达和激活，并且抑制或下调PKCalpha可阻断细胞松弛素D诱导的软骨形成。细胞松弛素D还下调了与软骨形成相关的Erk-1磷酸化。因此，我们的结果表明，肌动蛋白细胞骨架的破坏通过激活PKCalpha和抑制Erk-1信号传导来诱导间充质细胞的软骨形成。
