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

INTRODUCTION

We previously demonstrated that magnesium ions (Mg) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1α (HIF-1α)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1α, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg in OA treatment. This study aims to investigate the efficacy of combination of Mg 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, MgCl (0.5 mol/L), VC (3 mg/ml) or MgCl (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

Mg 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 Mg on HIF-1α expression in cartilage. Additionally, combination of Mg and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg and VC inhibited osteophyte formation and expressions of pain-related neuropeptides.

CONCLUSIONS

Intra-articular administration of Mg and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA.