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 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.
Yang
R
R
Department of Orthopaedics, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, Taiwan.
Fu
W
W
Wang
S
S
Liu
T
T
Lin-Shiau
S
S
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D003572:Cytochalasins / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005456:Fluorescent Dyes; D007476:Ionophores / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000633:toxicity*; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D002273:Carcinogens; D003572:Cytochalasins; D004075:Diglycerides; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007476:Ionophores; D013449:Sulfonamides; D014746:Vimentin; C049999:N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide; D000001:Calcimycin; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium