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Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis
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.
Insights
Matrix metalloproteinase 9 (MMP-9) levels in synovial fluid correlate with vascular patterns in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) stimulates MMP-9 production in synovial membranes.
Area of Science:
- Rheumatology and Immunology
- Cell Biology
- Angiogenesis Research
Background:
- Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF) are implicated in inflammatory arthritis.
- Synovial neovascularization patterns differ across arthritic conditions.
- Endothelial cell (EC) apoptosis plays a role in joint pathology.
Purpose of the Study:
- To investigate the relationship between MMP-9, VEGF, EC apoptosis, and synovial vascular patterns in early rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA).
- To determine the effect of VEGF on MMP-9 production in synovial membranes.
Main Methods:
- Analyzed synovial fluid (SF) and synovial membrane (SM) from 34 patients with early RA, PsA, and OA.
- Measured SF MMP-9 and VEGF levels using ELISA.
- Assessed EC apoptosis via TUNEL assay and MMP-9 expression via immunohistochemistry.
- Stimulated synovial tissue explants with VEGF and measured MMP-9 release.
Main Results:
- SF MMP-9 levels were significantly higher in early PsA than early RA.
- MMP-9 levels correlated with synovial vascular morphology and SF VEGF.
- VEGF stimulation significantly increased MMP-9 production in SM explants.
- EC apoptosis was more pronounced in early RA SM compared to early PsA SM.
Conclusions:
- SF MMP-9 levels are associated with neovascularization and VEGF levels in early inflammatory arthritis.
- VEGF directly stimulates MMP-9 production by synovial membranes.
- Differential EC apoptosis may contribute to distinct angiogenic patterns in RA and PsA.
