Abstract
There is a growing body of evidence supporting the use of intra-articular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti-inflammatory action has yet to be clarified. This study was undertaken to examine the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL-1 β, 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 cultures of SSF in the presence of IL-1 β. Gene expression levels were analyzed by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Intracellular production of COX-2 protein 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 the binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose-dependently decreased the 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 on expressions of proinflammatory cytokine mRNAs and COX-2/PGE2 production in IL-1-stimulated SSF. HA inhibited the expression of proinflammatory cytokine mRNAs and COX-2/PGE2 production via CD44 in IL-1-stimulated SSF derived from patients with rotator cuff disease. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease.
