OP0175 Monocarboxylate Transporter (MCT)-4, Associated with the Decrease of Synovial Fluid Ph, is A Novel Therapeutic Target of Rheumatoid Arthritis

Background It is well known that synovial fluid pH is decreased in rheumatoid arthritis (RA) patients (1), but the meaning and mechanism remain unclear. Objectives We investigate the correlation between synovial fluid pH and the disease activity of RA. We reveal the mechanism by which synovial fluid pH is regulated and explore the novel therapeutic strategy of RA by applying this mechanism. Methods We measured the values of pH and the concentration of L-lactate in synovial fluid of RA patients. Next, we investigated the expression of ion transporters regulating intracellular and extracellular pH in RA synovial fibroblasts (RASFs) obtained from the inflamed joints using quantitative RT-PCR and Western Blotting. Finally, we suppressed the ion transporter expression by small interfering RNA (siRNA) against the ion transporter increased in RASFs, and analyzed their viability and proliferative capacity of RASFs. Results Synovial fluid pH was decreased as the disease activity score (DAS)-28 CRP increased in RA patients (graph A, n=17, r = -0.81, p