GLUCOCORTICOIDS INHIBIT BONE-RESORPTION BY ISOLATED RAT OSTEOCLASTS BY ENHANCING APOPTOSIS

We have studied the effects of glucocorticoids on the activity and via bility of neonatal rat osteoclasts in vitro. In the bone slice assay, glucocorticoids caused a dose-dependent decrease in the amount of bone resorbed, which was accompanied by a parallel decrease in osteoclast number. Loss of osteoclasts was due to their death, which occurred by the process of apoptosis. Evidence for the latter was obtained by a ra nge of techniques, including time-lapse video microscopy, acridine ora nge staining, DNA fragment detection and transmission electron microsc opy. Immunocytochemistry revealed the presence of glucocorticoid recep tors in osteoclasts, and glucocorticoid-induced cell death could be pr evented by the glucocorticoid receptor antagonist, RU486. These observ ations suggest that glucocorticoids promote receptor-mediated apoptosi s of rat osteoclasts in vitro. This finding may help to explain recent data indicating that, in sharp contrast with their effects on the hum an skeleton, glucocorticoids inhibit bone resorption and increase bone mass in rats in vivo.