Osteoarthritic lesions: involvement of three different collagenases

Arthritis Rheum. 1997 Nov;40(11):2065-74. doi: 10.1002/art.1780401120.

Abstract

Objective: To assess the presence of fibroblast collagenase (MMP-1), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion.

Methods: Messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and Northern blot analysis.

Results: MMP-1 and MMP-13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP-8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP-1 and MMP-13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor alpha stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP-13.

Conclusion: These findings suggest a key role of MMP-13 and MMP-8, as well as MMP-1 in osteoarthritis.

Publication types

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

MeSH terms

  • Aged
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cartilage, Articular / enzymology*
  • Collagenases / analysis*
  • Collagenases / biosynthesis
  • Collagenases / genetics
  • DNA Primers / chemistry
  • Gene Expression / drug effects
  • Humans
  • Interleukin-1 / pharmacology
  • Male
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 8
  • Middle Aged
  • Osteoarthritis / enzymology*
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Swine
  • Tretinoin / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • DNA Primers
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Tretinoin
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 1