Clinical significance of levels of matrix metalloproteinases MMP-3 and MMP-1 in sera and synovial fluids in patients with rheumatoid arthritis and osteoarthritis

ABSTRACT

To investigate whether serum levels of matrix metalloproteinases [MMP-3, stromelysin] and [MMP-1, collagenase] are specifically elevated in joint disease as rheumatoid arthritis [RA] compared to osteoarthritis [OA] and to assess how these markers reflect the clinical activity of RA compared to circulating cytokine as tumor necrosis factor-alpha [TNF-alpha] as well as established variables as [C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]]. This study included 22 patients with RA, 10 patients with OA and 10 healthy control subjects matched for age and sex. Patients with superimposed infection were excluded. Serum levels of MMP-3, MMP-1, TNF-alpha and CRP were assayed. Synovial fluid [SF] levels of MMP-3 and MMP-1 were also assayed. Serum levels of TNF-alpha and CRP in RA patients were significantly higher than normal subjects. Serum MMP-1 was significantly elevated in patients with RA and OA, compared to healthy controls but there were no significant differences between patients with RA and those with OA. Serum MMP-3 levels did not differ between OA patients and normal sera. However, RA patients displayed significantly elevated levels of this enzyme, compared to OA and control sera. Levels of MMP-3 and MMP-1 in the SF of RA patients were significantly higher than in OA fluids. CRP, ESR, TNF-alpha and MMP-3 correlated significantly with the swollen joint count, The strongest positive correlations existed between rheumatoid activity as assessed by the levels of CRP and circulating levels of MMP-3. Similar correlations between TNF-alpfa concentration and CRP, MMP-1 and MMP-3 were observed in RA patients. Serum levels of MMP-3 correlated significantly with serum concentrations of MMP-l in RA patients [r = 0.487, p < 0.05]. There was close correlation between serum and SF concentrations of MMP-3 in RA patients [r = 0.619, p < 0.01]. In the same patients there was highly significant correlation between SF concentrations of MMP-3 and MMP-l [r= 0.732, p <0.001]. Our data suggested that elevated MMP-3 levels reflected disease activity of RA better than cytokine levels. MMP-3 may be seen as a constitutive marker of the pathological process underlying joint tissue degradation in RA