Role of Hyaluronic Acid in Post-traumatic Osteoarthritis: Experimental Validation in a Rat Model

Introduction: The pathogenesis of Post-traumatic Osteoarthritis (PTOA) remains incompletely understood. Although Hyaluronic Acid (HA) is widely used in the clinical management of Osteoarthritis (OA), its dynamic changes and mechanistic role in PTOA progression require further investigation. Aim: To characterise the dynamic changes of HA concentration in synovial fluid and serum during post-traumatic Knee OA (KOA) development using a rat model. Materials and Methods: The present Animal Randomised Controlled Trial (Animal RCT) was conducted in the laboratory of Longhua Central Hospital, Shenzhen, Guangdong Province, China, from August 2022 to July 2024. The present study utilised 36 male Sprague-Dawley rats (two-month-old, 320±20g). Rats were randomised into a sham control group (n=18; skin incision only) and Anterior Cruciate ligament Transection (ACLT) model group (n=18). Six subgroups (A-F) were established according to observation time points (postoperative days 7, 14, 21, 28, 70, and 98), each comprising three model and three control rats. Experimental procedures were temporally randomised, with collection of: Right hind-knee synovial fluid and serum for Enzyme-Linked Immunosorbent Assays (ELISA), right hindknee joint specimens for safranin O-fast green staining and immunohistochemical analysis of CD68+ macrophage infiltration. Statistical analyses employed linear regression curve fitting, descriptive statistics {mean±Standard Deviation (SD)}, Analysis of Variance (ANOVA), and Student’s t-test. A p-value <0.05 was considered significant. Results: Experimental groups exhibited progressive decline in synovial HA concentration with disease progression (p=0.028), reaching nadir levels at postoperative Day 70 (synovial fluid: 5.113±0.2478 ng/mL; serum: 6.671±0.8706 ng/mL), followed by modest recovery (Days 71-98). HA dynamics demonstrated significant negative correlations with IL-1 levels expression (r=- 0.5335, p<0.05). Conclusion: Post-traumatic joint instability induces sustained HA depletion (≤Day 70), potentially accelerating cartilage matrix degradation through Matrix Metalloproteinases (MMP)-13 upregulation and IL-1-mediated inflammatory cascades. These findings identify promising therapeutic targets for early PTOA intervention.