Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture
Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture
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DOI：
10.1016/j.ejphar.2006.02.030
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发表时间：
2006-04-24
影响因子：
5
通讯作者：
Schurman, L
中科院分区：
文献类型：
--
作者：
Cortizo, AM;Sedlinsky, C;Schurman, L
先前已确定失代偿性糖尿病与骨矿物质密度和/或质量损失之间存在关联。在这项研究中，我们评估了二甲双胍对培养成骨细胞生长和分化的影响。用二甲双胍（25-500 μ M）处理两种成骨细胞样细胞（UMR 106和MC 3 T3 E1）24小时，导致细胞增殖的剂量依赖性增加。二甲双胍还促进成骨细胞分化：它增加了两种细胞系中I型胶原的产生，并刺激了MC 3 T31成骨细胞中的碱性磷酸酶活性。此外，二甲双胍显著增加了3周MC 3 T3 E1培养物中矿化结节的形成。二甲双胍诱导磷酸化细胞外信号调节激酶（P-ERK）的激活和再分布，并剂量依赖性地刺激内皮细胞和诱导型一氧化氮合酶（e/iNOS）的表达。这些结果首次表明二甲双胍对培养成骨细胞的直接成骨作用，这可能是通过ERK-1/2的激活/重新分布和e/ NOS的诱导介导的。(c)2006 Elsevier B.V保留所有权利。
An association has been previously established between uncompensated diabetes mellitus and the loss of bone mineral density and/or quality. In this study, we evaluated the effects of metformin on the growth and differentiation of osteoblasts in culture Treatment of two osteoblast-like cells (UMR106 and MC3T3E1) with metformin (25-500 mu M) for 24h led to a dose-dependent increase of cell proliferation. Metformin also promoted osteoblastic differentiation: it increased type-I collagen production in both cell lines and stimulated alkaline phosphatase activity in MC3T31 osteoblasts. In addition, metformin markedly increased the formation of nodules of mineralization in 3-week MC3T3E1 cultures. Metformin induced activation and redistribution of phosphorylated extracellular signal-regulated kinase (P-ERK) in a transient manner, and dose-dependently stimulated the expression of endothelial and inducible nitric oxide synthases (e/iNOS). These results show for the first time a direct osteogenic effect of metformin on osteoblasts in culture, which could be mediated by activation/redistribution of ERK-1/2 and induction of e/ NOS.(c) 2006 Elsevier B.V All rights reserved.