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 (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.
Chowdhury
M H
MH
Division of Rheumatology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Moak
S A
SA
Rifkin
B R
BR
Greenwald
R A
RA
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002642:Chick Embryo; D004318:Doxycycline / Q000494:pharmacology; D006493:Heparin; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010010:Osteoclasts / Q000187:drug effects*; D013754:Tetracyclines / Q000494:pharmacology*
D013754:Tetracyclines; D006493:Heparin; D008666:Metalloendopeptidases; D004318:Doxycycline