Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis

Arthritis Rheum. 2001 Sep;44(9):2024-8. doi: 10.1002/1529-0131(200109)44:9<2024::AID-ART351>3.0.CO;2-K.


Objective: To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC) apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern.

Methods: Thirty-four patients underwent needle arthroscopy of the knee joint; 12 had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and 10 had osteoarthritis (OA). The early RA and early PsA patients were matched for disease activity. SF levels of MMP-9 and VEGF were measured by an enzyme-linked immunosorbent assay, and EC apoptosis was measured by TUNEL assay. MMP-9 expression was examined in SM by immunohistochemistry. Synovial tissue explants were stimulated with VEGF, and MMP-9 levels were measured in the supernatants. The synovial vascular pattern was recorded.

Results: SF MMP-9 levels were significantly higher in early PsA patients than in early RA patients; OA patients had minimal levels. MMP-9 levels correlated with blood vessel morphology and SF VEGF levels. MMP-9 expression was greater in early PsA SM than in early RA SM, but the difference was not significant. In contrast however, EC apoptosis was greater in early RA SM than in early PsA SM. MMP-9 levels increased 2-fold and 9-fold, respectively, in SM explant culture supernatants on day 7 in response to stimulation with 25 ng/ml and 50 ng/ml of VEGF.

Conclusion: SF MMP-9 levels correlate with the pattern of SM neovascularization and SF VEGF levels in early inflammatory arthritis, and VEGF increases MMP-9 production by SM. Endothelial cell apoptosis, however, appears to be more prevalent in early RA. This combination of factors may explain the pattern of differential angiogenesis in these arthritides.

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • Arthritis / metabolism
  • Arthritis / pathology*
  • Arthritis, Psoriatic / metabolism
  • Arthritis, Psoriatic / pathology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Biopsy
  • Cells, Cultured
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Lymphokines / analysis
  • Lymphokines / pharmacology
  • Male
  • Matrix Metalloproteinase 9 / analysis*
  • Middle Aged
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Synovial Fluid / chemistry
  • Synovial Fluid / enzymology
  • Synovial Membrane / blood supply
  • Synovial Membrane / enzymology
  • Synovial Membrane / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 9