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Tetracyclines Inhibit Connective Tissue Breakdown by Multiple Non-Antimicrobial Mechanisms

Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook, Stony Brook, NY

H.-M. Lee

Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook, Stony Brook, NY

M.E. Ryan

Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook, Stony Brook, NY

W.V. Giannobile

Departments of Periodontology, Harvard School of Dental Medicine and Forsyth Dental Center, Boston, MA

J. Payne

Department of Surgical Sciences, School of Dentistry, University of Nebraska Medical Center, Omaha, NE

T. Sorsa

Department of Periodontology and Medical Chemistry, University of Helsinki, Finland

A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected non-antimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a variety of dental (e.g., adult periodontitis) and medical (e.g., arthritis, osteoporosis, cancer) diseases. The site on the TC molecule responsible for its MMP-inhibitory activity was identified which led to the development of a series of chemically modified non-antimicrobial analogs, called CMTs, which also have therapeutic potential but do not appear to induce antibiotic side-effects. Longitudinal double-blind studies on humans with adult periodontitis have demonstrated that a sub-antimicrobial dose of doxycycline (previously reported to suppress collagenase activity in the periodontal pocket) is safe and effective and has recently been approved by the FDA as an adjunct to scaling and root planing.

Key Words: Non-antimicrobial tetracyclines • doxycycline • collagenase • matrix metalloproteinases • host modulation.

Advances in Dental Research, Vol. 12, No. 1, 12-26 (1998)
DOI: 10.1177/08959374980120010501


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