Combination of magnesium ions and Vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice
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AbstractIntroduction
We previously demonstrated that magnesium ions (Mg2+) 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 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-1α 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.
We previously demonstrated that magnesium ions (Mg2+) 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 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-1α 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.
Acceptance Date21/10/2020
All Author(s) ListHao Yao, Jiankun Xu, Jiali Wang, Yifeng Zhang, Nianye Zheng, Jiang Yue, Jie Mi, Lizhen Zheng, Bingyang Dai, Wenhan Huang, Shuhang Yung, Peijie Hu, Yechun Ruan, Qingyun Xue, Kiwai Ho, Ling Qin
Journal nameBioactive Materials
Year2021
Month5
Volume Number6
Issue Number5
PublisherElsevier
Pages1341 - 1352
eISSN2452-199X
LanguagesEnglish-United States
KeywordsOsteoarthritisMagnesiumVitamin CCartilageInflammationOsteophyte
