Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice
Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice
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DOI：
10.1172/jci8942
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发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Schmidt, AM
中科院分区：
文献类型：
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作者：
Lalla, E;Lamster, IB;Schmidt, AM
糖尿病与牙周病的患病率、严重程度和进展有关。为了验证这一假设，即激活的受体（晚期糖基化终产物）有助于糖尿病相关牙周炎的发病机制，我们处理糖尿病小鼠，感染人类牙周病原体牙龈卟啉单胞菌，可溶性唾液酸（saponin）。sRAGE是受体的细胞外结构域，可结合配体并阻断与细胞表面RAGE的相互作用和激活。阻断牙槽骨可剂量依赖性地减少牙槽骨丢失。此外，我们注意到牙龈组织中促炎细胞因子TNF-α和IL-6的产生减少，以及基质金属蛋白酶水平降低。在用sodium治疗的小鼠中，牙龈AGEs也减少，与观察到的牙槽骨丢失抑制平行。这些发现将过度和过度的炎症反应与糖尿病破坏性牙周病的发病机制联系起来。
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.