Calmodulin antagonists inhibit retinoic acid-induced cartilage degradation in vitro

Summary

In cultured fetal rat bones retinoic acid induces the release of proteoglycan, followed by cartilage tissue breakdown. This correlates with a shortening of the bone of up to 40%. The calmodulin antagonists trifluoperazine, chlorpromazine, diazepam and the naphthalenesulphonamide W-7 inhibited the retinoic acid-induced bone shortening. Inhibition by trifluoperazine and W-7 was noted at 40 and 75 μM, respectively, concentrations which were not cytotoxic as judged from³H-leucine incorporation into protein. Trifluoperazine and W-7 at the above concentrations did not affect the release of proteoglycan induced by retinoic acid, indicating that bone shortening is not necessarily linked with the release of proteoglycan. In consideration of our previous and present demonstrations that retinoic acid-induced cartilage resorption was inhibited by the ionophore A23187 and by calmodulin antagonists, we suggest that Ca²⁺ and calmodulin may be involved in the mediation of retinoic acid action in cartilage.