Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1

J Clin Invest. 1993 Jul;92(1):179-85. doi: 10.1172/JCI116547.

Abstract

We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cartilage, Articular / enzymology*
  • Collagenases / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Interleukin-1 / pharmacology*
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / metabolism*
  • Middle Aged
  • Molecular Weight
  • Organ Culture Techniques
  • RNA, Messenger / genetics

Substances

  • Interleukin-1
  • RNA, Messenger
  • Collagenases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9