Parathyroid hormone-induced calcium efflux from cultured bone is mediated by protein kinase C translocation

Stuart M. Sprague*, Mordecai M. Popovtzer, Michal Dranitzki-Elhalel, Hanna Wald

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Activa-tion of adenylate cyclase is believed to be the major intracellular mediator of bone rsorption induced by parathyroid hormone (PTH), prostaglandins, and various bone resorbing cytokines. Studies have demonstrated a dissociation between PTH-induced bone reorption and adenosine 3′,5′-cyclic monophosphate (cAMP) formation, as well as suggested a role of protein kinase C (PKC) in mediating in part the actions of PTH. We therefore investigated the relative contribution of the adenylate cyclase or PKC signal transduction pathways in mediating the PTH-induced net calcium release from cultured neonatal calvariae, an in vitro model of bone résorption. PTH (10-11 to 10-7 M) caused a dose-dependent increase in calcium efflux from cultured bone and activated both cAMP and PKC. To determine the role of each of these second messengers in mediating PTH-induced calcium release from bone, calvariae were preincubated with either the adenylate cyclase inhibitor SQ-22536 (10-5 to 10-4 M) or the PKC inhibitor staurosporine (10-7 M) before coincubation with PTH. Compared with control, PTH caused a significant calcium efflux, whereas preincubation with SQ-22536 had no effect on basal calcium efflux and partially inhibited the calcium efflux caused by PTH. In contrast preincubation with staurosporine completely obliterated the PTH-induced calcium efflux. PTH is a potent stimulator of calcium release and activates both the cAMP and PKC signal transduction pathways in cultured bone. Inhibition of PTH-stimulated PKC activity completely abolished the PTH-induced calcium efflux from calvariae, whereas PTH-induced calcium efflux persisted despite adenylate cyclase inhibition. Thus the bone resorbing effect of PTH appears to be dependent predominantly on activation of PKC.

Original languageAmerican English
Pages (from-to)F1139-F1146
JournalAmerican Journal of Physiology
Issue number6 PART 2
StatePublished - 1996
Externally publishedYes


  • 5′-cyclic monophosphate
  • Adenosine 3′
  • Bone resorption
  • Calvariae
  • Signal transduction


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