Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss
| العنوان: | Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss |
|---|---|
| المؤلفون: | Hao Yao, Yuwei Zhu, Wenxue Tong, Jiankun Xu, Bingyang Dai, Le Huang, Ling Qin, Dick Ho Kiu Chow, Xu Li |
| المصدر: | Bioactive Materials, Vol 6, Iss 8, Pp 2511-2522 (2021) Bioactive Materials |
| بيانات النشر: | KeAi Communications Co., Ltd., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Trabecular bone, medicine.medical_specialty, Bone loss, Simvastatin, Statin, medicine.drug_class, QH301-705.5, 0206 medical engineering, Biomedical Engineering, 02 engineering and technology, Bone resorption, Article, Biomaterials, chemistry.chemical_compound, Osteoclast, Internal medicine, Hyperlipidemia, medicine, Magnesium, Obesity, Biology (General), Magnesium ion, Materials of engineering and construction. Mechanics of materials, Bone mineral, Chemistry, Cholesterol, nutritional and metabolic diseases, 021001 nanoscience & nanotechnology, medicine.disease, 020601 biomedical engineering, Endocrinology, medicine.anatomical_structure, TA401-492, lipids (amino acids, peptides, and proteins), 0210 nano-technology, Biotechnology, medicine.drug |
| الوصف: | 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 (Mg2+) 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 Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ 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. Graphical abstract Illustration of the underlying mechanism of combined therapy of Mg2+ and simvastatin that leads to a synergistic effect on attenuating the high-fat diet-induced bone loss via impairing osteoclast maturation and bone resorption in bone marrow. Meanwhile, the combination can directly limit the hepatocytic synthesis of cholesterol.Image 1 Highlights • High-fat diet-fed mouse has a susceptibility to lower trabecular bone mass as compared with that of normal-fat diet-fed mouse. • The combination of Mg2+ and simvastatin attenuates the trabecular bone loss in high-fat diet-fed mice. • The combination of Mg2+ and simvastatin reduces the hepatocytic synthesis of cholesterol. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63d92fad78e391676f099b7274efa924 http://www.sciencedirect.com/science/article/pii/S2452199X21000396 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....63d92fad78e391676f099b7274efa924 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |