Regulation of advanced glycation end product (AGE) receptors and apoptosis by AGEs in osteoblast-like cells
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Advanced glycation end products (AGEs) have been proposed as the pathological mechanisms underlying diabetic chronic complications. They may also play a role in the pathogenesis of diabetic osteopenia, although their mechanisms of action remain unclear. We investigated the protein (immunofluorescence) and gene expression (realtime RT-PCR) of two receptors for AGEs, RAGE and galectin-3, as well as their regulation by AGEs, and the apoptotic effect on osteoblast-like cells (UMR106 and MC3T3E1) in culture. AGEs up-regulated the expression of RAGE and galectin-3 in both cells lines. These effects were accompanied by an increase in the corresponding mRNA in the non-tumoral MC3T3E1 but not in the osteosarcoma UMR106 cells. Finally, we demonstrated that a 24 h exposure to AGEs induced apoptosis in both cell lines. Thus, AGEs-receptors may play important roles in the bone alterations described in aging and diabetic patients.
KeywordsAdvanced glycation end products RAGE Galectin-3 Osteoblasts Apoptosis AGE-receptors Regulation
This work was partially supported by grants from Universidad Nacional de La Plata, Ministerio de Salud y Acción Social de la Nación (Subsecretaría de Investigación y Tecnología, Beca Ramón Carrillo-Arturo Oñativia) and CICPBA to AMC, and grant R01 GM070589-01 from the NIGMS, National Institutes of Health to GRV. NM is a fellow of CONICET, SBE is a member of the Carrera del Investigador, CONICET, and AMC is a member of the Carrera del Investigador, CICPBA.
- 3.Thornalley PJ (1998) Cell activation by glycated proteins. AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand) 44:1013–1023Google Scholar