Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells
Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells
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二甲双胍增强人绒毛膜绒毛间充质干细胞的成骨作用并抑制脂肪形成
DOI：
10.1620/tjem.241.13
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发表时间：
2017-01-01
影响因子：
2.2
通讯作者：
Shi, Qin
中科院分区：
文献类型：
--
作者：
Gu, Qiaoli;Gu, Yanzheng;Shi, Qin
二甲双胍是治疗2型糖尿病常用的一线降糖药物。最近的研究表明，二甲双胍可以通过诱导内皮型一氧化氮合酶（eNOS）来促进骨形成。人绒毛膜间充质干细胞（CV-MSCs）是再生医学的理想候选细胞。本研究旨在观察二甲双胍对人CV-MSCs成骨和成脂分化的影响，并探讨其作用机制。将从人足月胎盘制备的CV-MSC与不同浓度的二甲双胍一起培养。用0.05 mM二甲双胍处理72小时对CV-MSC的增殖没有明显影响。因此，将CV-MSC在补充有0.05 mM二甲双胍的成骨培养基中培养7天或14天。二甲双胍治疗7天可增加成骨蛋白mRNA的表达水平，包括碱性磷酸酶、runt相关转录因子2和骨桥蛋白。二甲双胍还增强CV-MSCs的矿化。二甲双胍诱导CV-MSCs成骨分化过程中eNOS表达。相比之下，当CV-MSC在成脂培养基中培养14天时，0.05 mM二甲双胍抑制成脂蛋白mRNA的表达，包括增殖物激活受体-γ和CCAAT/增强子结合蛋白-α。二甲双胍治疗后28天，脂滴蓄积也减少。这些发现表明二甲双胍可以增强CV-MSC的成骨分化并减少脂肪细胞形成。二甲双胍对CV-MSCs成骨分化的影响可能与eNOS表达有关。我们的研究结果将突出二甲双胍在骨质疏松症和骨折中的治疗潜力。
Metformin is the first-line anti-hyperglycemic drugs commonly used to treat type 2 diabetes. Recent studies have shown that metformin can enhance bone formation through induction of endothelial nitric oxide synthase (eNOS). Human chorionic villous mesenchymal stem cells (CV-MSCs) are promising candidates for regenerative medicine. The present study aimed to investigate the effects of metformin on the osteogenic and adipocytic differentiation of human CV-MSCs, and to elucidate the underlying mechanism. CV-MSCs, prepared from human term placentae, were cultured with different concentrations of metformin. Treatment for 72 hours with 0.05 mM metformin had no noticeable effect on the proliferation of CV-MSCs. Consequently, CV-MSCs were cultured for seven or 14 days in the osteogenic medium supplemented with 0.05 mM metformin. Treatment for seven days with metformin increased the expression levels of osteogenic protein mRNAs, including alkaline phosphatase, runt-related transcription factor 2, and osteopontin. Metformin also enhanced the mineralization of CV-MSCs. Furthermore, metformin induced the expression of eNOS in CV-MSCs during osteogenic differentiation. By contrast, when CV-MSCs were cultured for 14 days in the adipogenic medium, 0.05 mM metformin inhibited the expression of adipogenic protein mRNAs, including proliferators-activated receptor-gamma and CCAAT/enhancer binding protein-alpha. The lipid droplet accumulation was also reduced on 28 days after metformin treatment. These findings indicate that metformin can enhance osteogenic differentiation of CV-MSCs and reduce adipocyte formation. The effect of metformin on osteogenic differentiation of CV-MSCs may be associated with eNOS expression. Our findings will highlight the therapeutic potential of metformin in osteoporosis and bone fracture.