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

  • Bone and Cartilage
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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 μg/ml, which was reversed by Dox, 5 μg/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.

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Authors and Affiliations

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

    M. H. Chowdhury, S. A. Moak & R. A. Greenwald (Chief of Rheumatology)

  2. New York University School of Dental Medicine, New York, NY, USA

    B. R. Rifkin

Authors
  1. M. H. Chowdhury
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  2. S. A. Moak
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  3. B. R. Rifkin
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  4. R. A. Greenwald
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The Long Island Campus for the Albert Einstein College of Medicine

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Chowdhury, M.H., Moak, S.A., Rifkin, B.R. et al. Effect of tetracyclines which have metalloproteinase inhibitory capacity on basal and heparin-stimulated bone resorption by chick osteoclasts. Agents and Actions 40, 124–128 (1993). https://doi.org/10.1007/BF01976761

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  • DOI: https://doi.org/10.1007/BF01976761

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