Serum MMP-3 in rheumatoid arthritis

Rheumatoid arthritis (RA) is a disease raised by synovial proliferation. Overgrown synovium leads to secrete inflammatory cytokines and various kinds of proteinases. Chondrocyte and synovicyte activated by inflammatory cytokines produce extracellular matrix metalloproteinases (MMPs). Among MMPs, matrix metalloproteinase-3 (MMP-3; stromelysin-1) is considered to be the most important proteinases since MMP-3 localizes in erosive cartilage and it has a wide range of substrate specificity. Recently a one-step sandwich enzyme immunoassay (EIA) system for MMP-3 was developed and then several other assay kits have been also used clinically. A lot of clinical data of serum MMP-3 levels measured by these EIA kits have been reported. We review these clinical data of MMP-3 in various diseases and consider that the serum MMP-3 value could be a useful marker for grasping pathology of bone damage and diagnosis for RA. Serum MMP-3 levels in RA patients have been reported to be higher than healthy controls. From these clinical data, MMP-3 may reflect joint destruction and it would be valuable to predict bone damage progression, especially in the early stage of RA. The anti-cytokine therapy such as anti-TNF-α antibody and TNF-α receptor down-regulates serum MMP-3 levels in RA patient. This may suggest that MMP-3 is a useful marker for follow-up of anti-cytokine therapy. Two EIA systems for serum MMP-3, namely, PANACLEAR MMP-3[Plate] and MMP-3[BS], have been approved in Japan as diagnostic tool for RA. The value determined by each kit is different, but correlates each other. To compare with both clinical data, we recommend to convert them with the regression coefficient and to use MMP-3 value for clinical practice.