Intra-articular injection of magnesium chloride attenuates osteoarthritis progression in rats

Objective: To explore the effects of Mg²⁺ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg²⁺ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM). Design: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl₂ (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450–500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl₂ (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl₂ was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg²⁺ in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg²⁺ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg²⁺ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg²⁺ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. Conclusion: Intra-articular injections of Mg²⁺ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.