Blockade of RAGE suppresses periodontitis-associated bone loss in diabeticmice

Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Re ceptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected w ith the human periodontal pathogen Porphyromonas gingivalis, with soluble R AGE (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 TN F-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sR AGE, paralleling the observed suppression in alveolar bone loss. These find ings link RAGE and exaggerated inflammatory responses to the pathogenesis o f destructive periodontal disease in diabetes.