MECHANISM OF THE MORPHOLOGICAL-CHANGES INDUCED BY STAUROSPORINE IN RAT OSTEOBLASTS

Protein kinase C (PKC) plays an important role in the differentiation of cells, however, little is known about its relationship to bone meta bolism. We have previously demonstrated that staurosporine concentrati on 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 b y staurosporine. The morphological changes induced by staurosporine we re inhibited by microtubule depolymerizers or elevated intracellular c alcium, however, actin depolymerizers enhanced the effects of staurosp orine. Fluorescence labeling showed that staurosporine caused the diss olution of the actin microfilaments, but left the microtubules and vim entin filaments intact. PKC activators partially antagonized the morph ological changes induced by staurosporine. Inhibition of protein kinas e A or calmodulin-dependent kinase is less effective in the induction of stellate cell formation. These results suggest that the morphologic al changes of osteoblasts induced by staurosporine may be partly due t o PKC inhibition, but other mechanisms may also be involved.