ABSTRACT
Matrix metalloproteinases [MMPs] are cytokine-modulated enzymes that play an important role in the pathogenesis of RA by inducing bone resorption and cartilage destruction. Tissue inhibitors of metalloproteinases [TIMPs] are naturally occurring MMPs inhibitors. In rheumatoid arthritis [RA], there is a disturbed balance between MMPs and TIMPs favoring proteolysis. This study was performed to evaluate the significance of measuring the serum and synovial fluid [SF] levels of MMP-3 and TIMPs in RA and osteoarthritis [OA] patients in an attempt to provide more insight in their role in the pathogenesis of those two diseases. Serum levels of MMP-3 and TIMP-1 were measured from 30 RA, 20 OA patients and 20 healthy controls using double-antibody ELISA. Also, their levels were measured in the SF of 14 RA and 9 OA patients. RA disease activity was assessed using the Multivariate Analysis of Mallya and Mace and joint erosions were assessed using Larsen score. Serum and SF levels of MMP-3 and TIMP-1 were significantly higher in RA than OA patients and in OA patients than controls. Their levels were significantly higher in the SF than in the serum. Serum and SF TIMP-1: MMP-3 ratio was significantly lower in RA as compared to OA patients and normal controls and this ratio was significantly lower in the SF than in the serum of RA patients. Serum levels of MMP-3 and TIMP-1 correlated strongly with clinical and laboratory parameters of rheumatoid disease activity, and the serum levels of MMP-3 showed a significant positive correlation with the number of joint erosions but TIMP-1 levels did not show this positive correlation. Serum and SF MMP-3 and TIMP-1 levels were significantly higher in RA than OA patients and normal controls. They appear to play a critical role in joint inflammation and destruction, especially MMP-3, which may serve as an additional marker for assessment of RA disease activity and severity