Effects of indomethacin on the production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by human articular chondrocytes

Harumoto Yamada, Toshiyuki Kikuchi, Osamu Nemoto, Ken'ichi Obata, Hiroshi Sato, Motoharu Seiki, Masayuki Shinmei

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Abstract

Objective. To study the action of indomethacin on cartilage catabolic activity by comparing the production of a matrix degrading proteinase and its inhibitor in human articular chondrocyte cultures. Methods. Matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP1) in conditioned medium from human articular chondrocyte cultures were measured using a one-step sandwich enzyme immunoassay. TIMP-1 mRNA expression was analyzed by Northern blotting using a 0.6 kb cDNA probe for human TIMP-1. Results. Human recombinant interleukin 1β (IL-1β) increased MMP-3 levels in primary chondrocyte cultures. Indomethacin at 10-5 M inhibited this IL-1β stimulation, but had no effect in the therapeutic range (10-6-10-7 M). Low levels of indomethacin (10-7 M) significantly increased the production of TIMP-1 by chondrocytes. Synthesis of TIMP-1 appeared to be inhibited by prostaglandin E2 (PGE2), since exogenously added PGE2 reversed the stimulating effect of indomethacin on TIMP-1 production. Northern blot analysis showed that 10-7 M indomethacin increased TIMP-1 mRNA levels in chondrocytes. Conclusion. Our findings indicate that low levels of indomethacin can benefit matrix metabolism by affecting the balance of proteinases to their inhibitors in human articular cartilage.

Original languageEnglish
Pages (from-to)1739-1743
Number of pages5
JournalJournal of Rheumatology
Volume23
Issue number10
Publication statusPublished - 24-10-1996
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Yamada, H., Kikuchi, T., Nemoto, O., Obata, K., Sato, H., Seiki, M., & Shinmei, M. (1996). Effects of indomethacin on the production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by human articular chondrocytes. Journal of Rheumatology, 23(10), 1739-1743.