非诺贝特通过下调高脂饮食诱导的 2 型糖尿病模型小鼠的 Runx2 降低骨质量。
Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model.
机构信息
Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, People's Republic of China.
State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory of Molecular Medicine and School of Medicine, Nanjing University, No. 22 Hankou Road, Gulou District, Nanjing, Jiangsu Province, 210093, China.
出版信息
Lipids Health Dis. 2017 Oct 13;16(1):201. doi: 10.1186/s12944-017-0592-5.
BACKGROUND
This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model.
METHODS
T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2, caspase 3, and osteoblast marker genes were detected by RT-qPCR.
RESULTS
The biomechanical properties of bones from DIO-FENO group were significantly lower than those in the control and DIO-PBS groups. Besides, the trabecular number was lower than those of the other groups, though the cortical porosity was decreased compared with that of DIO-PBS group because of the increase of apoptotic cells. The expression of osteocalcin and collagen I were decreased after treatment with fenofibrate in T2DM mice. Moreover, the cell viability was decreased after treated with different concentrations of fenofibrate, and the expression of Runx2 decreased after treated with high dose of fenofibrate.
CONCLUSION
Fenofibrate decreases the bone quality of T2DM mice through decreasing the expression of collagen I and osteocalcin, which may be resulted from the down regulation of Runx2 expression.
背景
本研究旨在探讨非诺贝特对 2 型糖尿病（T2DM）小鼠模型骨质量的影响。
方法
通过高脂肪饮食诱导 T2DM 小鼠模型，并用非诺贝特（100mg/kg）（DIO-FENO）或 PBS（DIO-PBS）处理 4 周。通过 micro-CT 和 3 点弯曲试验分析股骨的骨微结构和生物力学特性。通过免疫组织化学染色和 Western blot 检测蛋白质表达。通过 TUNEL 染色评估细胞凋亡。通过 RT-qPCR 检测 Bcl2、caspase 3 和成骨细胞标志物基因。
结果
DIO-FENO 组的骨生物力学性能明显低于对照组和 DIO-PBS 组。此外，与其他组相比，DIO-FENO 组的骨小梁数量较低，尽管由于凋亡细胞的增加，皮质孔隙率降低。与 DIO-PBS 组相比，在用非诺贝特治疗的 T2DM 小鼠中，骨钙素和胶原 I 的表达降低。此外，用不同浓度的非诺贝特处理后细胞活力降低，用高剂量非诺贝特处理后 Runx2 的表达降低。
结论
非诺贝特通过降低胶原 I 和骨钙素的表达降低 T2DM 小鼠的骨质量，这可能是由于 Runx2 表达下调所致。
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