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Agents Actions. 1993 Sep;40(1-2):124-8.

Effect of tetracyclines which have metalloproteinase inhibitory capacity on basal and heparin-stimulated bone resorption by chick osteoclasts.

Author information

1
Division of Rheumatology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.

Abstract

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

PMID:
8147268
DOI:
10.1007/bf01976761
[Indexed for MEDLINE]

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