Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms.

L. M. Golub, H. M. Lee, M. E. Ryan, W. V. Giannobile, J. Payne, T. Sorsa

Research output: Contribution to journalReview article

492 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12-26
Number of pages15
JournalAdvances in dental research
Volume12
Issue number2
StatePublished - Nov 1998

Fingerprint

Tetracyclines
Connective Tissue
Chronic Periodontitis
Collagenases
Matrix Metalloproteinases
Root Planing
Periodontal Pocket
Doxycycline
Double-Blind Method
Osteoporosis
Arthritis
Tooth
Anti-Bacterial Agents
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Golub, L. M., Lee, H. M., Ryan, M. E., Giannobile, W. V., Payne, J., & Sorsa, T. (1998). Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Advances in dental research, 12(2), 12-26.

Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. / Golub, L. M.; Lee, H. M.; Ryan, M. E.; Giannobile, W. V.; Payne, J.; Sorsa, T.

In: Advances in dental research, Vol. 12, No. 2, 11.1998, p. 12-26.

Research output: Contribution to journalReview article

Golub, LM, Lee, HM, Ryan, ME, Giannobile, WV, Payne, J & Sorsa, T 1998, 'Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms.', Advances in dental research, vol. 12, no. 2, pp. 12-26.
Golub, L. M. ; Lee, H. M. ; Ryan, M. E. ; Giannobile, W. V. ; Payne, J. ; Sorsa, T. / Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. In: Advances in dental research. 1998 ; Vol. 12, No. 2. pp. 12-26.
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