Alone or in combination, hyaluronic acid and chondroitin sulfate alleviate ECM degradation in osteoarthritis by inhibiting the NF-κB pathway.

Backgrounds: Osteoarthritis (OA) significantly impacts the elderly, leading to disability and decreased quality of life. While hyaluronic acid (HA) and chondroitin sulfate (CS) are recognized for their therapeutic potential in OA, their effects on extracellular matrix (ECM) degradation are not well understood. This study investigates the impact of HA and CS, individually and combined, on ECM degradation in OA and the underlying mechanisms. Methods: OA was modeled in rats through anterior cruciate ligament transection and in cells using IL-1β pretreatment. Treatments included HA and CS, alone or combined, with and without PMA (an NF-κB pathway activator). Cartilage tissue was analyzed using HE and Saffron O-fast green staining, with degradation assessed via the OARSI score. Inflammatory factors were measured by ELISA, and ECM-related proteins were detected by immunohistochemistry, immunofluorescence, and Western blotting. Chondrocyte viability was assessed using CCK8. Results: HA and CS treatments significantly reduced cartilage damage, decreased inflammatory factor release, alleviated ECM degradation, and inhibited NF-κB pathway activation compared to the OA group (P < 0.05). The combination of HA and CS further enhanced these therapeutic effects (P < 0.05). However, these benefits were reversed when PMA was introduced (P < 0.05). Conclusion: HA and CS, whether used alone or in combination, mitigate ECM degradation in osteoarthritis by inhibiting the NF-κB pathway, offering potential therapeutic benefits for OA management. [ABSTRACT FROM AUTHOR]