Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.
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.
Lalla
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E
Division of Periodontics, School of Dental and Oral Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. el94@columbia.edu
Lamster
I B
IB
Feit
M
M
Huang
L
L
Spessot
A
A
Qu
W
W
Kislinger
T
T
Lu
Y
Y
Stern
D M
DM
Schmidt
A M
AM
D016301:Alveolar Bone Loss / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010518:Periodontitis / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000472:pathogenicity; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9