Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells
Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells
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DOI：
10.1211/jpp.60/12.0017
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发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Hu, Jing
中科院分区：
文献类型：
--
作者：
Gao, Ying;Xue, Jing;Hu, Jing
2型糖尿病是一种常见的糖尿病。在这项研究中，我们评估了二甲双胍对培养的大鼠骨髓间充质干细胞（MSCs）的成骨细胞和脂肪细胞分化的影响。用100 μ M二甲双胍在成骨细胞或脂肪细胞培养基中处理MSCs 21天，导致MSCs中成骨细胞标志物的mRNA表达增加，但脂肪细胞标志物的mRNA表达减少。二甲双胍明显刺激矿化结节的沉积，并阻止细胞质脂滴的形成。此外，核心结合因子a1（Cbfa1）和过氧化物酶体增殖物激活受体γ 2（PPAR γ 2）蛋白的碱性磷酸酶活性和蛋白质印迹分析也证实了二甲双胍抑制脂肪细胞分化并促进成骨细胞分化。成骨细胞和成脂细胞分化之间的相互关系表明，二甲双胍可能通过抑制PPAR γ来调节成骨细胞和成脂细胞分化。
Metformin is widely used for the treatment of type 2 diabetes mellitus. In this study, we evaluated the effects of metformin on the osteoblast and adipocyte differentiation of rat marrow mesenchymal stem cells (MSCs) in culture, Treatment of MSCs in osteoblastic or adipogenic medium with 100 mu M metformin for 21 days led to an increased mRNA expression of the osteoblast markers but a decreased mRNA expression of the adipocyte markers in the MSCs. Metformin markedly stimulated deposition of mineralized nodules and blocked the formation of cytoplasmic lipid droplets. In addition, alkaline phosphate activity and Western blot analysis for core binding factor a1 (Cbfa1) and peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) proteins also confirmed that metformin inhibited adipocyte differentiation and promoted osteoblast differentiation. The reciprocal relationship between osteoblastic and adipogenic differentiation suggests that metformin may regulate osteoblastic and adipogenic differentiation through inhibition of PPAR gamma.