Objective: Matrix metalloproteinase (MMP) is a novel proteolytic enzyme that plays an important role in joint destruction in rheumatoid arthritis (RA). To elucidate the dynamics of MMPs in serum and synovial fluid, we measured the concentration and activity of MMP-1, -9, -13 in serum and synovial fluid of RA patients. Among them especially we focused on newly defined MMP-13 and compared with MMP-1 and MMP-9.
Methods: Serum, synovial fluid and synovial, and pannus tissues used in this study were obtained from RA patients. To compare the dynamics of each enzymic protein, we performed the following procedures: Firstly, we measured concentration of MMP-1, -9, -13 by using ELISA kit. Secondly, the activity of MMP-1, -9, -13 were also measured by using the MMP activity assay system. Then we obtained the activity ratio of each MMP from calculation of activity/concentration. We also examined the expression of MMP-13 in synovial tissues by immunohistochemical and in situ hybridization studies.
Result: Concentration and activity levels of MMP-1, -9, -13 were significantly higher in RA serum and synovial fluid than in OA. Activity ratio of MMP-1, MMP-9 MMP-13 were 3.60 +/- 1.56, 1.03 +/- 1.75, 35.30 +/- 24.28 (ODA450/ng) in RA serum and 1.60 +/- 2.02, 3.97 +/- 14.83, 14.25 +/- 15.04 (ODA450/ng) in synovial fluid. In synovial and pannus tissues. MMP-13 positive cells were diffusely demonstrated by immunohistochemical and in situ hybridization studies. They were synovial lining cells, endothelial cells, fibroblasts, monocytes, osteoblasts, and chondrocytes.
Conclusion: MMP-13 positive cells were diffusely presented in joint regions including synovial and pannus tissues. Although the concentration of MMP-13 was not so high, its activity ratio was elevated in serum and synovial fluid in the patients with rheumatoid arthritis.