Oral bacterium contributes to periodontal inflammation by forming advanced glycation end products.

Abstract

The oral bacterium Tannerella forsythia is associated with periodontitis, an inflammatory disease affecting tooth-supporting tissues. The bacterium produces a dicarbonyl compound, methylglyoxal (MGO), whose levels correlate with the severity of periodontitis. MGO can induce inflammation directly or via the generation of glycation products called advanced glycation end products (AGEs). T. forsythia-produced MGO has been shown to cause tissue collagen glycation, which in turn can induce pro-inflammatory cytokine secretion in monocytes via receptor for advanced glycation end product (RAGE) receptor activation. The current study investigated the impact of T. forsythia-secreted MGO on human gingival fibroblasts and endothelial cells. For assessing the in vivo impact of T. forsythia-secreted MGO, we employed an oral gavage-induced mouse model of periodontitis utilizing the wild-type and MGO-deficient strains of T. forsythia. Our results showed that the apoptotic activity was enhanced, and cell migration was reduced in fibroblasts exposed to collagen treated with the T. forsythia wild-type culture supernatant. Moreover, monocyte binding, reactive oxygen species production, and inflammatory cytokine secretion were increased in fibroblasts, and neutrophil transendothelial migration was enhanced in response to the T. forsythia wild type-treated collagen. In vivo, increased AGE accumulation in gingival tissues with increased alveolar bone loss was observed in wild-type T. forsythia as compared to the MGO-deficient strain-infected mice. These data demonstrated that T. forsythia-secreted MGO contributes to periodontal tissue destruction by mitigating gingival fibroblast-mediated tissue healing and promoting endothelial cell dysfunction. These findings provide a basis for targeting the T. forsythia-associated AGE-RAGE axis in alleviating periodontitis.