Cyclosporine A inhibits bone resorption in cultured neonatal mouse calvaria

Abstract

The effect of the immunosuppressive agent cyclosporine A (CsA) on the resorption of neonatal mouse calvaria was examined in vitro. CsA, at concentrations of 10(-7) to 3 X 10(-5) M, inhibited bone resorption produced by 10(-8) M parathyroid hormone, 3 U/ml of mouse recombinant interleukin-1,5 X 10(-7) M prostaglandin E2, 14 U/ml of thrombin, 5 micrograms/ml of bacterial lipopolysaccharide or 10(-9) M 1 alpha,25-dihydroxyvitamin D3. The effects of CsA on resorption were maintained over 72 h of culture with parathyroid hormone or prostaglandin E2 with no evidence of "escape". Removal of CsA from the cultures resulted in recovery of the resorptive response after a 24-h delay. CsA did not affect thymidine incorporation into DNA in the calvaria. Our results demonstrate that CsA is a nonselective antiresorptive agent in bone, with actions that differ somewhat from those of calcitonin. The results confirm and extend our previous findings on effects of CsA in fetal rat limb bones, with the exception that the inhibitory effects of CsA were more rapidly and completely reversible in the limb bone system.