Potent collagenase inhibitors prevent interleukin-1-induced cartilage degradation in vitro

Int J Tissue React. 1991;13(5):237-41.


The matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, contribute to the destruction of articular cartilage which occurs during rheumatoid and osteoarthritis. Ro 31-4724, a substrate analogue containing a hydroxamic acid function, is a potent but non-selective inhibitor of all three MMPs (I50, collagenase = 10 nM), whereas Ro 31-7467, a phosphinic acid transition-state analogue, shows 14-fold and 12-fold selectivity for collagenase (I50 = 17 nM) over gelatinase and caseinase (stromelysin) respectively. The effects of these inhibitors on interleukin-1-induced bovine nasal cartilage degradation were examined. The hydroxamate Ro 31-4724 inhibits proteoglycan and collagen loss, whereas the phosphinic acid Ro 31-7467 selectively inhibits collagen breakdown in this model. This represents the first demonstration of potent and selective inhibition of IL1-induced cartilage degradation in vitro by MMP inhibitors. These results suggest that collagenase is responsible for collagen loss and that a different enzyme, possibly stromelysin, is responsible for proteoglycan degradation in this model.

MeSH terms

  • Animals
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cattle
  • Cells, Cultured
  • Gelatinases
  • Hydroxamic Acids / pharmacology*
  • Interleukin-1 / pharmacology*
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases / physiology
  • Microbial Collagenase / antagonists & inhibitors*
  • Microbial Collagenase / physiology
  • Pepsin A / physiology
  • Phosphinic Acids / pharmacology*


  • Hydroxamic Acids
  • Interleukin-1
  • Phosphinic Acids
  • Pepsin A
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Microbial Collagenase