Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice

Introduction: We previously demonstrated that magnesium ions (Mg2+) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1 alpha (HIF-1 alpha)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1 alpha, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg2+ in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg2+ in OA treatment. This study aims to investigate the efficacy of combination of Mg2+ and VC on alleviating joint destruction and pain in OA. Material and methods: Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline, MgCl2 (0.5 mol/L), VC (3 mg/ml) or MgCl2 (0.5 mol/L) plus VC (3 mg/ml) at week 2 post-operation, twice weekly, for 2 weeks. Joint pain and pathological changes were assessed by gait analysis, histology, western blotting and micro-CT. Results: Mg2+ and VC showed additive effects to significantly alleviate the joint destruction and pain. The efficacy of this combined therapy could sustain for 3 months after the last injection. We demonstrated that VC enhanced the promotive effect of Mg2+ on HIF-1 alpha expression in cartilage. Additionally, combination of Mg2+ and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg2+ and VC inhibited osteophyte formation and expressions of pain-related neuropeptides. Conclusions: Intra-articular administration of Mg2+ and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA.

Automated summary

The combination therapy of magnesium ions and vitamin C significantly alleviated joint destruction and pain in osteoarthritis, with sustained effects for up to 3 months. Vitamin C enhanced the promotive effect of magnesium ions on HIF-1 alpha expression in cartilage, and the combination also promoted M2 polarization of macrophages in the synovium.