Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss  

作　　者：Bingyang Dai Xu Li Jiankun Xu Yuwei Zhu Le Huang Wenxue Tong Hao Yao Dick Ho-kiu Chow Ling Qin 

机构地区：[1]Musculoskeletal Research Laboratory of Department of Orthopedics&Traumatology and Innovative Orthopaedic Biomaterial&Drug Translational Research Laboratory,Li Ka Shing Institute of Health Sciences,The Chinese University of Hong Kong,Hong Kong,China [2]Department of Chemistry,The Chinese University of Hong Kong,New Territories,Hong Kong,China

出　　处：《Bioactive Materials》2021年第8期2511-2522,共12页生物活性材料（英文）

基　　金：supported by Theme-based Research Scheme from RGC-Hong Kong(No.T13-402/17N);partially supported by Health and Medical Research Fund(17180671);National Natural Science Foundation of China(81802152).

摘　　要：Introduction:Magnesium(Mg)has a prophylactic potential against the onset of hyperlipidemia.Similar to statin,Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass.The combination of statin with Mg ions(Mg^(2+))may be able to alleviate the high-fat diet(HFD)-induced bone loss and reduce the side-effects of statin.This study aimed to explore the feasibility of combined Mg^(2+)with simvastatin(SIM)for treating HFD-induced bone loss in mice and the involving mechanisms.Materials and methods:C57BL/6 male mice were fed with a HFD or a normal-fat diet(NFD).Mice were intraperitoneally injected SIM and/or orally received water with additional Mg^(2+)until sacrificed.Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates.Bone mineral density(BMD)and microarchitecture were assessed by micro-computed tomography(μCT)in different groups.The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.Results:μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8.The cortical thickness in HFD-fed group had a significant decrease at week 24,as compared with NFD-fed group.The combination of Mg^(2+)and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption.Besides,such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13(Mmp13)mRNA expression in pre-osteoclasts.Conclusions:The combination of Mg^(2+)and SIM shows a synergistic effect on attenuating the HFD-induced bone loss.Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

关 键 词：OBESITY Bone loss MAGNESIUM SIMVASTATIN Trabecular bone CHOLESTEROL 

分 类 号：R68[医药卫生—骨科学]