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Exp Clin Endocrinol Diabetes 2008; 116(6): 333-340
DOI: 10.1055/s-2007-992786
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

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

L. Schurman 1 , A. D. McCarthy 2 , C. Sedlinsky 1 , M. V. Gangoiti 2 , V. Arnol 2 , L. Bruzzone 3 , A. M. Cortizo 2
  • 1Centro de Endocrinología y Metabolismo, Hospital Francés, Buenos Aires
  • 2Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata
  • 3División Química Analítica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata
Weitere Informationen

Publikationsverlauf

received 09.08.2007 first decision 09.10.2007

accepted 15.10.2007

Publikationsdatum:
14. Februar 2008 (online)

Auch verfügbar auf
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Abstract

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.

Key words

metformin - advanced glycation end product - osteoblasts - oxidative stress - RAGE

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Correspondence

Prof. Dr. A. M. Cortizo

Cátedra de Bioquímica Patológica

Facultad de Ciencias Exactas

Universidad Nacional de La Plata

47 y 115

1900 La Plata

Argentina

Telefon: 54/221/423 53 33 ext 49/33

Fax: 54/221/422 34 09

eMail: cortizo@biol.unlp.edu.ar