Comparison of parathyroid hormone and calcium ionophore A23187 effects on bone resorption and nucleic acid synthesis in cultured fetal rat bone

Summary

It has recently been demonstrated that calcium ionophore A23187 mimics certain of the effects of parathyroid hormone (PTH) on bone in vitro, including stimulation of⁴⁵Ca release and cAMP formation. To further examine the relative effects of these two agents on bone cell metabolism, we compared the effects of synthetic PTH 1–34 (50 ng/ml) and calcium ionophore A23187 (0.5µg/ml) on⁴⁵Ca release, DNA concentration, and nucleic acid synthesis in fetal rat forelimb rudiments cultured for periods up to 120 h. Both agents stimulated⁴⁵Ca release; however, the effects of PTH were apparent after a shorter period of exposure. Bone DNA concentration (expressed asµg DNA/mg bone) was not affected by PTH but was significantly increased relative to control values by exposure to A23187 for 8–120 h of incubation. PTH increased the incorporation of³H-thymidine into DNA at 30 and 48 h, and increased the incorporation of¹⁴C-uridine into RNA at 48 h, time points which corresponded to a period of accelerated PTH stimulation of⁴⁵Ca release. In contrast,³H-thymidine and¹⁴C-uridine incorporation were both uniformly suppressed by A23187 at all time points examined. Thus the increased DNA concentration observed in A23187-treated rudiments appeared to be the result of a decreased rate of bone maturation and mineralization. The markedly different patterns of nucleic acid synthesis in response to PTH and A23187 suggest that these agents differ significantly in their mechanisms of action on bone cell metabolism.