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

Evanthia Lalla, Ira B. Lamster, Michael Feit, Linda Huang, Alexandra Spessot, Wu Qu, Thomas Kislinger, Yan Lu, David Stern, Ann Marie Schmidt

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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-α 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.

Original languageEnglish (US)
Pages (from-to)1117-1124
Number of pages8
JournalJournal of Clinical Investigation
Volume105
Issue number8
DOIs
StatePublished - Jan 1 2000

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Periodontitis
Bone and Bones
Alveolar Bone Loss
Periodontal Diseases
Porphyromonas gingivalis
Cell Surface Receptors
Matrix Metalloproteinases
Interleukin-6
Advanced Glycosylation End Product-Specific Receptor
Cytokines
Ligands

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lalla, E., Lamster, I. B., Feit, M., Huang, L., Spessot, A., Qu, W., ... Schmidt, A. M. (2000). Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. Journal of Clinical Investigation, 105(8), 1117-1124. https://doi.org/10.1172/JCI8942

Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. / Lalla, Evanthia; Lamster, Ira B.; Feit, Michael; Huang, Linda; Spessot, Alexandra; Qu, Wu; Kislinger, Thomas; Lu, Yan; Stern, David; Schmidt, Ann Marie.

In: Journal of Clinical Investigation, Vol. 105, No. 8, 01.01.2000, p. 1117-1124.

Research output: Contribution to journalArticle

Lalla, E, Lamster, IB, Feit, M, Huang, L, Spessot, A, Qu, W, Kislinger, T, Lu, Y, Stern, D & Schmidt, AM 2000, 'Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice', Journal of Clinical Investigation, vol. 105, no. 8, pp. 1117-1124. https://doi.org/10.1172/JCI8942
Lalla, Evanthia ; Lamster, Ira B. ; Feit, Michael ; Huang, Linda ; Spessot, Alexandra ; Qu, Wu ; Kislinger, Thomas ; Lu, Yan ; Stern, David ; Schmidt, Ann Marie. / Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 8. pp. 1117-1124.
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