Metformin Reverts Deleterious Effects of Advanced Glycation End-Products (AGEs) on Osteoblastic Cells

• Autores: Schurman, León; McCarthy, Antonio Desmond; Sedlinsky, Claudia; Gangoiti, Maria Virginia; Arnol, Verónica; Bruzzone, Liliana; Cortizo, Ana María
• Año de publicación: 2007
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Bioquímica y Biología Molecular; Metformin; Advanced glycation end product; Osteoblasts; Oxidative stress; RAGO
• Institución: Comisión de Investigaciones Científicas de la Provincia de Buenos Aires

Advanced glycation endproducts (AGEs) are implicated in the complications of diabetes and ageing, affecting several tissues, including bone. Metformin, an insulin-sensitizer drug, reduces the risk of life-threatening macrovascular complications. We have evaluated the hypothesis that metformin can abrogate AGE-induced deleterious effects in osteoblastic cells in culture. In two osteoblast-like cell lines (UMR106 and MC3T3E1), AGE-modifi ed albumin induced cell death, caspase- 3 activity, altered intracellular oxidative stress and inhibited alkaline phosphatase activity. Metformin-treatment of osteoblastic cells prevented these AGE-induced alterations. We also assessed the expression of AGE receptors as a possible mechanism by which metformin could modulate the action of AGEs. AGEs-treatment of osteoblast-like cells enhanced RAGE protein expression, and this up-regulation was prevented in the presence of metformin. Although the precise mechanisms involved in metformin signaling are still elusive, our data implicate the AGE-RAGE interaction in the modulation of growth and differentiation of osteoblastic cells.