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Eur J Pharmacol. 2006 Apr 24;536(1-2):38-46. Epub 2006 Feb 28.

Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture.

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Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, and Centro de Endocrinología y Metabolismo, Hospital Francés, Buenos Aires, Argentina.


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 microM) for 24 h 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 MC3T3E1 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/iNOS.

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