期刊
BIOACTIVE MATERIALS
卷 6, 期 5, 页码 1341-1352出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2020.10.016
关键词
Osteoarthritis; Magnesium; Vitamin C; Cartilage; Inflammation; Osteophyte
资金
- Hong Kong RGC Theme-based Research Scheme [T13-402/17-N]
- National Natural Science Foundation of China [81802152]
- Collaborative Research Fund [C4026-17WF]
- Health and Medical Research Fund [17180671]
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.
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.
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