EFFECT OF TETRACYCLINES WHICH HAVE METALLOPROTEINASE INHIBITORY CAPACITY ON BASAL AND HEPARIN-STIMULATED BONE-RESORPTION BY CHICK OSTEOCLASTS

Several tetracyclines (TETs) are potent inhibitors of collagenase (CGa se) and can inhibit connective tissue degradation in a variety of infl ammatory and degenerative disorders. The role of CGase in bone resorpt ion by osteoclasts (OC) remains unclear. Disaggregated OCs from chick embryos were cultured for 24 h on devitalized bovine cortical bone + h eparin in the presence of various TETs. Doxycycline (Dox) inhibited pi t formation in a dose-dependent manner. CMT, a TET derivative which in hibits matrix metalloproteinases (MMPs) but is not antimicrobial, also inhibited chick OC bone resorption. Heparin markedly stimulated bone resorption at 5 mug/ml, which was reversed by Dox, 5 mug/ml. TETs can reversibly inhibit both basal and heparin-stimulated bone resorption b y chick OCs. These findings suggest that MMPs may play a role in osteo clastic bone resorption, and that safe and effective inhibitors of MMP s, including certain TETs, might have a potential therapeutic role.