Reversible suppression by ionophore A23187 of retinoic acid-induced cartilage resorption in cultured fetal rat bones.

In fetal rat bones in culture the divalent cation ionophore A23187 inhibited in a dose-dependent manner both the release of proteoglycans and the subsequent degradation of cartilage induced by retinoic acid, indicating that calcium was involved in its action. A23187 had to be present continuously to manifest its inhibitory effect; retrieval of the ionophore abolished the suppression, demonstrating that the effect was reversible and not due to toxicity. A23187 at 1.0 μM, which completely blocked the retinoic acid-induced cartilage resorption, markedly suppressed3H-leucine,3H-mannose and3H-thymidine incorporation in control and retinoic acid-treated cultures. Reduced3H-thymidine incorporation did not appear to be responsible for the inhibition by A23187 of retinoic acid-induced cartilage resorption because inhibitors of DNA synthesis did not affect the retinoic acid response. In the presence of retinoic acid the ionophore at 0.3 μM had no effect on the incorporation of3H-leucine and3H-mannose, but suppressed the retinoic acid-induced proteoglycan release. This suggests that reduced protein and glycoprotein synthesis were not the main causes for the inhibitory effect of A23187. In conclusion, retinoic acid-induced cartilage degradation required calcium at some crucial points.