Abstract
Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Receptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected with the human periodontal pathogen Porphyromonas gingivalis, with soluble RAGE (sRAGE). sRAGE is the extracellular domain of the receptor, which binds ligand and blocks interaction with, and activation of, cell-surface RAGE. Blockade of RAGE diminished alveolar bone loss in a dose-dependent manner. Moreover, we noted decreased generation of the proinflammatory cytokines TNF-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sRAGE, paralleling the observed suppression in alveolar bone loss. These findings link RAGE and exaggerated inflammatory responses to the pathogenesis of destructive periodontal disease in diabetes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alveolar Bone Loss / etiology
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Alveolar Bone Loss / immunology
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Alveolar Bone Loss / metabolism
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Alveolar Bone Loss / prevention & control*
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Animals
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Bacteroidaceae Infections / complications
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Bacteroidaceae Infections / etiology*
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Bacteroidaceae Infections / immunology
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Bacteroidaceae Infections / metabolism
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Diabetes Mellitus, Experimental / complications*
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Disease Models, Animal
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Glycation End Products, Advanced / administration & dosage
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Glycation End Products, Advanced / metabolism*
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Humans
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Interleukin-6 / metabolism
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Male
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 3 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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Mice
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Mice, Inbred C57BL
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Periodontitis / complications
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Periodontitis / etiology*
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Periodontitis / immunology
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Periodontitis / metabolism
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Porphyromonas gingivalis / immunology
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Porphyromonas gingivalis / pathogenicity
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / immunology
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Receptors, Immunologic / physiology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Glycation End Products, Advanced
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Interleukin-6
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic
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Tumor Necrosis Factor-alpha
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9