Effects of Intra-Articular Administration of High-Molecular-Weight Linear Hyaluronic Acid on Synovial Fluid Characteristics and Joint Environment

Synovitis is an inflammatory disorder in horses that contributes to cartilage degradation and osteoarthritis. This study evaluated the effects of intra-articular administration of high-molecular-weight (HMW), linear (non-cross-linked) hyaluronic acid (HA) in an equine model of lipopolysaccharide (LPS)-induced acute synovitis. In this randomized blinded study, acute synovitis was induced in radiocarpal joints of 16 adult horses using LPS (0.25 ng). After 12 h, joints were treated intra-articularly with either 2 mL of phosphate-buffered saline (PBS; control group) or 2 mL of HMW-HA (20 mg/mL; 2280 kDa; treatment group). Horses underwent orthopedic, ultrasonographic, and synovial fluid evaluations. Horses treated with HMW-HA exhibited lower synovial membrane thickening and reduced lameness scores compared with controls. Synovial fluid analysis demonstrated increased concentrations of HMW-HA during the acute inflammatory phase in treated joints. Reduced chondroitin sulfate release was also detected following HMW-HA administration. Lower lipid peroxidation levels (TBARS) were observed in the treated group at 24 h and 14 days. Intra-articular administration of high-molecular-weight linear hyaluronic acid was associated with increased synovial availability of HMW-HA during the acute inflammatory phase, attenuation of pain-related clinical signs and synovial membrane thickening, and modulation of the redox environment. These findings support a modulatory role of linear HMW-HA in the intra-articular environment.