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

The oral bacterium <i>Tannerella forsythia</i> 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). <i>T. forsythia</i>-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 <i>T. forsythia</i>-secreted MGO on human gingival fibroblasts and endothelial cells. For assessing the <i>in vivo</i> impact of <i>T. forsythia</i>-secreted MGO, we employed an oral gavage-induced mouse model of periodontitis utilizing the wild-type and MGO-deficient strains of <i>T. forsythia</i>. Our results showed that the apoptotic activity was enhanced, and cell migration was reduced in fibroblasts exposed to collagen treated with the <i>T. forsythia</i> 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 <i>T. forsythia</i> wild type-treated collagen. <i>In vivo</i>, increased AGE accumulation in gingival tissues with increased alveolar bone loss was observed in wild-type <i>T. forsythia</i> as compared to the MGO-deficient strain-infected mice. These data demonstrated that <i>T. forsythia</i>-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 <i>T. forsythia</i>-associated AGE-RAGE axis in alleviating periodontitis.