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

Nitric Oxide Synthase Type III Nitric Oxide Synthase Type II Osteoblastos Collagen Type I Cell Line 03 medical and health sciences Diabetes mellitus Osteogenesis Cell Line, Tumor Metformin; Osteoblast; Osteoporosis; Diabetes mellitus Diabetes Mellitus Animals Hypoglycemic Agents Phosphorylation Metformina Ciencias Exactas Cell Proliferation Mitogen-Activated Protein Kinase 1 0303 health sciences Mitogen-Activated Protein Kinase 3 Osteoblasts Dose-Response Relationship, Drug Osteoblast Ciencias Químicas Cell Differentiation Alkaline Phosphatase Metformin Microscopy, Fluorescence Osteoporosis
DOI: 10.1016/j.ejphar.2006.02.030 Publication Date: 2006-03-01T18:46:10Z
ABSTRACT
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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