The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis

Karen Hasty, Robert A. Reife, Andrew Kang, John Stuart

Research output: Contribution to journalArticle

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Abstract

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen‐induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus‐cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chondrocytes were incubated with various concentrations of interleukin‐1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3‐fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin‐1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin‐specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.

Original languageEnglish (US)
Pages (from-to)388-397
Number of pages10
JournalArthritis & Rheumatism
Volume33
Issue number3
DOIs
StatePublished - Jan 1 1990

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Matrix Metalloproteinase 3
Arthritis
Cartilage
Chondrocytes
Proteoglycans
Joints
Caseins
Collagen Type II
Synovial Membrane
Frozen Sections
Articular Cartilage
Collagenases
Enzymes
Northern Blotting
Culture Media
Proteins
Western Blotting
Gels
Staining and Labeling
Inflammation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. / Hasty, Karen; Reife, Robert A.; Kang, Andrew; Stuart, John.

In: Arthritis & Rheumatism, Vol. 33, No. 3, 01.01.1990, p. 388-397.

Research output: Contribution to journalArticle

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