Production of Matrix Metalloproteinase (MMP-2, 9) from Cultured Human Synovial Cells

Gelatinase activity was assayed in conditioned media from synovial cells cultured from 16 patients with knee joint injury, osteoarthritis (OA) and rheumatoid arthritis (RA) . Production of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was measured to examine the role of gelatinase in arthrosis-related changes. Using culture supernatant, reactive areas were measured by gelatin zymography. Western blotting demonstrated the production of MMP-9 in all patients. Production of MMP-2 was detected in 9 of 16 patients. MMP-9 production did not differ significantly between the young-age, OA group and RA groups. When RA patients with nonproliferative synovitis due to burnout of inflammation were excluded, MMP-9 production in patients with grade 0, I or II articular destruction was significantly lower than that in those with grade III, IV or V articular destruction, suggesting an association between MMP-9 produced by synovial cells and articular destruction. The response to tumor necrosis factor-α (TNF-α) at 5U/ml of cultured synovial cell production of MMP-9 was not significantly different between the young-age group and OA group, but was significantly higher in both the young-age group and OA group when compared to that in the RA group. Response to interleukin 1-β (IL-1β) at 5U/ml of MMP-9 production was not significantly different when the young-age group was compared to the OA or the RA group, but was significantly higher in OA patients than in RA patients. In patients with RA, the findings suggested that production of MMP-9 by synovial cells is not influenced by TNF-α or IL-1β derived from inflammatory cells but is up-regulated by unknown mechanisms.