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

Hao 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

doi:10.1016/j.bioactmat.2020.10.016

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

Bioact Mater. 2020 Nov 10;6(5):1341-1352. doi: 10.1016/j.bioactmat.2020.10.016. eCollection 2021 May.

Authors

Hao Yao^{1

2}, Jiankun Xu^{1

2

3}, Jiali Wang⁴, Yifeng Zhang⁵, Nianye Zheng^{1

2}, Jiang Yue^{1

2}, Jie Mi^{1

2}, Lizhen Zheng^{1

2}, Bingyang Dai^{1

2}, Wenhan Huang^{1

2}, Shuhang Yung¹, Peijie Hu⁶, Yechun Ruan⁶, Qingyun Xue⁷, Kiwai Ho¹, Ling Qin^{1

2

3}

Affiliations

¹ Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
² Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong, China.
³ Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Hong Kong, China.
⁴ School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, PR China.
⁵ School of Life Science and Technology, Shanghai Tech University, Shanghai, PR China.
⁶ Department of Biomedical Engineering, Polytechnic University of Hong Kong, Hong Kong, China.
⁷ Department of Orthopedics, Beijing Hospital, No. 5th Clinical Medical Collage, Health Science Center, Peking University, Beijing, PR China.

Abstract

Introduction: 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.

Keywords: Cartilage; Inflammation; Magnesium; Osteoarthritis; Osteophyte; Vitamin C.