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

Abstract 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/PGE 2 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. PGE 2 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/PGE 2 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