Evidence for metalloproteinase inhibitor imbalance in human osteoarthritic cartilage

D. D. Dean, J. Martel-Pelletier, J. P. Pelletier, D. S. Howell, J. F. Woessner

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Abstract

Cartilage specimens from tibial plateaus, obtained from 13 osteoarthritic (OA) patients and seven controls, were selected from three regions: zone A, center of fibrillated area; zne B, area adjacent to fibrillation, and zone C, remote region of plateau. Acid and neutral metalloproteinases and tissue inhibitor of metalloproteinase (TIMP) were extracted with 2 M guanidine. Methods were developed to selectively destroy either proteinases or TIMP to prevent cross-reaction during assay. Acid and neutral proteinases were elevated ~150% in OA; TIMP was elevated ~50%. A positive correlation (r = 0.50) was found between acid and neutral proteinase activities in OA, but not in controls. Both proteinases were elevated two- to threefold in zones A, B, and C. However, the self-active form of the acid metalloproteinase was elevated only in zones A and B (200%); it correlated well with the Mankin scores, whereas the total activities did not. TIMP was elevated (50%) only in zones A and B. Both the proteinase levels and the Mankin score were elevated to a greater extent in the medial, than in the lateral, compartment. Titration of TIMP against the two metalloproteinases indicates that there is a small excess of inhibitor over enzymes in normal cartilage. In OA, TIMP does not increase to the same extent as the proteinases; the resultant excess of proteinases over TIMP may contribute to cartilage breakdown.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalJournal of Clinical Investigation
Volume84
Issue number2
DOIs
Publication statusPublished - Jan 1 1989

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ASJC Scopus subject areas

  • Medicine(all)

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Dean, D. D., Martel-Pelletier, J., Pelletier, J. P., Howell, D. S., & Woessner, J. F. (1989). Evidence for metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. Journal of Clinical Investigation, 84(2), 678-685. https://doi.org/10.1172/JCI114215