Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.

Abstract

The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 ,uM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, la-hydroxycholecalciferol, 3-isobutyl-l-methylxanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 ,ug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH-or calcitonintreated calvaria. We conclude that the ionophores A23187 or X-537A do not stimulate bone resorption

Interaction of Diphenylhydantoin (Phenytoin) and Phenobarbital with Hormonal Mediation of Fetal Rat Bone Resorption In Vitro

“…However, they were unable to demonstrate any effect of DPH on cAMP generation. The basis for the divergence of these results from the findings of the present studies is unclear, but could be the result of species differences, recently demonstrated differences in the responsitivity of calvaria and long bones to certain resorptive stimuli (27), or merely to differences in the concentrations of drug employed.…”

Interleukin-6 attenuates agonist-mediated calcium mobilization in murine osteoblastic cells.

“…However, in the absence of more direct assays of src activity, the possibility ofother intracellular TKs mediating 160-140-0 = 120-11 10 9 -LOG [PTHJ osteoblasts. Others and we have shown that the pleiotropic functions of these hormones on bone metabolism can be explained on the basis of antagonistic effects between the Ca2+ and cAMP signaling pathways (41)(42)(43)(44)56). With respect to cell growth, the cAMP messenger system is antiproliferative, while…”

“…It is now well established that the osteoblast plays a key role in both bone formation and bone resorption processes stimulated by osteotropic agents (39,40). Moreover, the Ca2' and cAMP messenger systems generated inside the osteoblastic cytosol mediate many of the effects of calciotropic hormones (41)(42)(43)(44). Given the in vivo observation of cooperativity between IL-6 and calciotropic hormones on bone remodeling, it is conceivable that the cytokine impinges on transduction pathways generated by hormones.…”

Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria.

“…Neonatal mouse calvaria were placed in organ culture as free-floating bones as described (16)(17)(18). The medium was Dulbecco's modified Eagle's medium supplemented with heat-inactivated (60°C for 1 hr) horse serum (final concentration, 15%).…”

“…Medium was changed at this time, and fresh control medium or medium containing specific treatments was added. Bone resorption was determined by measuring the release of calcium (40Ca2+) from the calvaria into the medium at 48 hr after addition of bone resorptionstimulating factors or drugs (16,17).…”