Increasing Intrinsic Hyaluronic Acid and Down-regulation of Inflammation Markers in Synovial Fluid from Patients with Knee Osteoarthritis may be Associated with Symptom Relief after Intra-articular Injection of Hyaluronic Acid

Abstract Background: Hyaluronic acid (HA) is the most common intra-articular therapy used to treat mild to moderate osteoarthritis (OA). However, the mechanism involved in this treatment is still not fully understood. The aim of the present study was to examine the effect and the possible mechanism of intra-articular HA (IAHA) injection in patients with knee osteoarthritis (OA).Methods: Twenty-eight patients with Kellgren–Lawrence scale II to III were enrolled in this study. All patients underwent ultrasound-guided injection using three consecutive weekly IAHA. Functional ability and pain were determined by the Western Ontario and McMaster University Index (WOMAC) questionnaire and visual analog scale (VAS). Further, the levels of HA, metalloproteinase (MMP)-1, MMP-3, MMP-13, interleukin (IL)-1β and IL-6 in synovial fluid were determined weekly before HA injection. Results: Functional improvement and pain relief were observed 4 weeks after treatment. At week 4, a significant increase of HA concentration was found, and the concentration of inflammatory cytokines including IL-1β, and IL-6, as well as matrix MMP-3 and MMP-13 significantly decreased. However, no significant difference was observed in MMP-1 level. Conclusion: These results suggest that increasing HA accumulation in synovial fluid may be associated with disease relief after weekly IAHA injection in patients with knee OA.