Calcitonin causes a sustained inhibition of protein kinase c-stimulated bone resorption in contrast to the transient inhibition of parathyroid hormone-induced bone resorption.
Calcitonin is a well known inhibitor of osteoclastic bone resorption, both in vivo and in vitro. However, it is also known that calcitonin has only a transient inhibitory effect on bone resorption. The mechanism for this so-called "escape from inhibition" phenomenon is not clear. In the present study, the inhibitory effect of calcitonin on phorbol ester-induced bone resorption was examined in cultured neonatal mouse calvaria. Bone resorption was assessed as the release of radioactivity from bones prelabelled in vivo with 45Ca. Two protein kinase C-activating phorbol esters, phorbol-12-myristate-13-acetate and phorbol-12,13-dibutyrate, both stimulated 45Ca release in 120-h cultures at a concentration of 10 nmol/l. Calcitonin (30 nmol/l) inhibited phorbol ester-stimulated bone resorption without any "escape from inhibition". This was in contrast to the transient inhibitory effect of calcitonin on bone resorption stimulated by parathyroid hormone (10 nmol/l), prostaglandin E2 (2 mumol/l), and bradykinin (1 mumol/l). Our results suggest that activation of protein kinase C produces a sustained inhibitory effect of calcitonin on bone resorption.
Ransjö
M
M
Department of Orthodontics, University of Umeå, Sweden.
Lerner
U H
UH
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced*; D001920:Bradykinin / Q000494:pharmacology; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D051379:Mice; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D010281:Parathyroid Hormone; D010703:Phorbol Esters; D002116:Calcitonin; D011493:Protein Kinase C; D015232:Dinoprostone; D001920:Bradykinin