Dai Bingyang, Li Xu, Xu Jiankun, Zhu Yuwei, Huang Le, Tong Wenxue, Yao Hao, Chow Dick Ho-Kiu, Qin Ling
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.
Department of Chemistry, The Chinese University of Hong Kong, New Territories, Hong Kong, China.
Bioact Mater. 2021 Feb 3;6(8):2511-2522. doi: 10.1016/j.bioactmat.2021.01.027. eCollection 2021 Aug.
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) 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 with simvastatin (SIM) for treating HFD-induced bone loss in mice and the involving mechanisms.
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 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.
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 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 () mRNA expression in pre-osteoclasts.
The combination of Mg 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.
镁（Mg）对高脂血症的发生具有预防潜力。与他汀类药物类似，镁被推荐作为高胆固醇血症的降脂药物，并且与骨量增加有关。他汀类药物与镁离子（Mg）联合使用可能能够减轻高脂饮食（HFD）诱导的骨质流失，并减少他汀类药物的副作用。本研究旨在探讨镁与辛伐他汀（SIM）联合治疗高脂饮食诱导的小鼠骨质流失的可行性及其相关机制。
将C57BL/6雄性小鼠分为高脂饮食组或正常脂肪饮食组（NFD）。小鼠腹腔注射SIM和/或口服补充镁的水，直至处死。采用酶联免疫吸附测定法检测血清和肝裂解物中的细胞因子和胆固醇。通过微型计算机断层扫描（μCT）评估不同组的骨密度（BMD）和微观结构。在各种处理下对棕榈酸预处理的HepG2细胞进行脂肪生成实验。
μCT分析显示，自第8周起，高脂饮食喂养组的小梁骨量显著低于正常脂肪饮食喂养组。与正常脂肪饮食喂养组相比，高脂饮食喂养组在第24周时皮质厚度显著降低。镁和SIM的联合使用通过抑制破骨细胞形成和骨吸收，显著减轻了高脂饮食喂养小鼠的小梁骨丢失。此外，这种联合使用还降低了肝细胞胆固醇的合成，并抑制了前破骨细胞中（）mRNA的表达。
镁和SIM联合使用对减轻高脂饮食诱导的骨质流失具有协同作用。我们目前的配方可能是一种经济有效的替代治疗方法，适用于肥胖相关的骨质流失。
