Tumor necrosis factor α and epidermal growth factor regulation of collagenase and stromelysin in adult porcine articular chondrocytes

Peter G. Mitchell, Herman S. Cheung

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Chondrocyte-derived metalloproteases have been postulated to play a role in the degradation of articular cartilage during the development of chronic arthritic disorders. TNFα (tumor necrosis factor alpha), an inflammatory mediator released by activated macrophages, has been detected in the synovial fluid of patients with rheumatoid diseases. We have found that TNFα is a potent stimulator of collagenase and stromelysin mRNA accumulation, collagenase activity, and immunoprecipitable stromelysin in monolayer cultures of adult porcine articular chondrocytes. In contrast EGF (epidermal growth factor), which stimulates collagenase and/or stromelysin synthesis in fibroblast systems, stimulated minimal amounts of these enzymes at both the message and protein levels. Nuclear run-on transcription analysis demonstrated that the TNFα-stimulated increase in stromelysin and collagenase message levels was, at least partially, due to increased transcription. Elevated transcription of these genes, in response to TNFα, was apparent by at least 2 hours post-stimulation. The degree of c-fos and c-jun stimulation by TNFα or EGF did not correlate with the levels of collagenase and stromelysin message stimulated by these factors. EGF stimulated significant accumulation of both c-fos and c-jun mRNAs while only very low amounts of these messages were stimulated by TNFα. Our data suggests that TNFα may contribute to articular cartilage degradation by stimulating chondrocyte-derived matrix metal loproteases. In addition the regulation of metalloprotease genes in chondrocytes may be different from their regulation in fibroblasts.

Original languageEnglish (US)
Pages (from-to)132-140
Number of pages9
JournalJournal of Cellular Physiology
Volume149
Issue number1
DOIs
StatePublished - Oct 1991
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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