Yang R, Fu W, Wang S, Liu T, Lin-Shiau S
Department of Orthopaedics, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, Taiwan.
Calcif Tissue Int. 1997 Jul;61(1):68-73. doi: 10.1007/s002239900297.
Protein kinase C (PKC) plays an important role in the differentiation of cells, however, little is known about its relationship to bone metabolism. We have previously demonstrated that staurosporine concentration dependently transformed the cultured rat osteoblasts into stellate cells. In this study, we further investigated the possible mechanisms and significance of the morphological changes of osteoblasts induced by staurosporine. The morphological changes induced by staurosporine were inhibited by microtubule depolymerizers or elevated intracellular calcium, however, actin depolymerizers enhanced the effects of staurosporine. Fluorescence labeling showed that staurosporine caused the dissolution of the actin microfilaments, but left the microtubules and vimentin filaments intact. PKC activators partially antagonized the morphological changes induced by staurosporine. Inhibition of protein kinase A or calmodulin-dependent kinase is less effective in the induction of stellate cell formation. These results suggest that the morphological changes of osteoblasts induced by staurosporine may be partly due to PKC inhibition, but other mechanisms may also be involved.
蛋白激酶C(PKC)在细胞分化中起重要作用,然而,其与骨代谢的关系却鲜为人知。我们之前已经证明,星形孢菌素浓度依赖性地将培养的大鼠成骨细胞转化为星状细胞。在本研究中,我们进一步探讨了星形孢菌素诱导成骨细胞形态变化的可能机制及意义。微管解聚剂或细胞内钙升高可抑制星形孢菌素诱导的形态变化,然而,肌动蛋白解聚剂可增强星形孢菌素的作用。荧光标记显示,星形孢菌素导致肌动蛋白微丝溶解,但微管和波形蛋白丝保持完整。PKC激活剂部分拮抗星形孢菌素诱导的形态变化。抑制蛋白激酶A或钙调蛋白依赖性激酶对星状细胞形成的诱导作用较小。这些结果表明,星形孢菌素诱导的成骨细胞形态变化可能部分归因于PKC抑制,但也可能涉及其他机制。