Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase-2/prostaglandin E2 production via CD44 in interleukin-1-stimulated subacromial synovial fibroblasts from patients with rotator cuff disease

A growing body of evidence supports use of intraarticular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti-inflammatory action has not been clarified. We examined the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL-1β, IL-6, and TNF-α and COX-2/PGE2 production in IL-1-stimulated subacromial-synovium fibroblasts (SSF) derived from patients with rotator cuff disease. Various concentrations of HA were added to monolayer SSF cultures in the presence of IL-1β. Gene expression levels were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Intracellular production of COX-2 was identified by Western blotting. PGE2 concentrations in the culture media were measured by ELISA. CD44 blocking with OS/37 was performed to investigate the mechanism of action of HA. Immunofluorescence cytochemistry confirmed binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose-dependently decreased expression of proinflammatory cytokine mRNAs and COX-2/PGE2 production in IL-1-stimulated SSF. Pretreatment with OS/37 reversed the inhibitory effects of HA. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1032–1037, 2008