Receptor for advanced glycation end products, inflammation, and accelerated periodontal disease in diabetes: mechanisms and insights into therapeutic modalities.
In hyperglycemic states found in diabetics, a nonenzymatic glycation and oxidation of proteins and lipids occurs. As a result, advanced glycation end products (AGEs), particularly N epsilon-(carboxymethyl)lysine, accumulate in the plasma and tissues of diabetic subjects. This accumulation has been linked to the development of pathogenic complications of diabetes. Many of the effects of AGEs are receptor-dependent and involve a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. The best characterized of these is the receptor for advanced glycation end products (RAGE), which is expressed by multiple cell types including endothelium and mononuclear phagocytes. Based on data from a variety of sources, including studies of RAGE-deficient mice, it appears that RAGE plays a central role in oral infection, exaggerated inflammatory host responses, and destruction of alveolar bone in diabetes. It is possible that antagonists of RAGE might have a valuable adjunctive therapeutic role for the management of periodontal disease found in diabetics.
Lalla
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School of Dental & Oral Surgery, Columbia University, New York, New York, USA.
Lamster
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Stern
D M
DM
Schmidt
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AM
D016301:Alveolar Bone Loss / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010510:Periodontal Diseases / Q000097:blood / Q000378:metabolism*; D010518:Periodontitis / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D007136:Immunoglobulins; D008024:Ligands; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine