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Publication : Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.

First Author  Lalla E Year  2000
Journal  J Clin Invest Volume  105
Issue  8 Pages  1117-24
PubMed ID  10772656 Mgi Jnum  J:61671
Mgi Id  MGI:1355408 Doi  10.1172/JCI8942
Citation  Lalla E, et al. (2000) Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. J Clin Invest 105(8):1117-24
abstractText  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.
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