Metformin reverts deleterious effects of advanced glycation end-products (AGEs) on osteoblastic cells.
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-modified 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.
Schurman
L
L
Centro de Endocrinología y Metabolismo, Hospital Francés, Buenos Aires.
McCarthy
A D
AD
Sedlinsky
C
C
Gangoiti
M V
MV
Arnol
V
V
Bruzzone
L
L
Cortizo
A M
AM
D000818:Animals; D001859:Bone Neoplasms; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000378:metabolism*; D007700:Kinetics; D008687:Metformin / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012516:Osteosarcoma; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism
D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D008687:Metformin