Porphyromonas Gingivalis and Dextran Sulfate Sodium Induce Periodontitis Through the Disruption of Physical Barriers in Mice

Periodontitis is a chronic inflammatory disease caused by the interaction of plaque-associated bacteria with host cells. Gingival epithelial barriers provide the first line of defense against plaque-associated bacteria, the primary cause of periodontitis. To investigate the role of physical barriers in the pathogenesis of periodontitis, dextran sulfate sodium (DSS), a tight junction (TJ)-disrupting chemical, was applied onto the gingival mucosa of mice in the absence or presence of Porphyromonas gingivalis, and alveolar bone loss was measured. The levels of the TJ proteins ZO-1 and JAM-1, the number of T cells, and the presence of bacteria within gingival tissue were examined by immunohistochemistry and in situ hybridization, respectively. In addition, oral bacterial communities were analyzed by pyrosequencing. Here, we show that both DSS and P. gingivalis induced alveolar bone loss accompanied by the reduced ZO-1 expression in the junctional epithelia. This reduction in ZO-1 expression was associated with increased levels of bacteria and T cells within the gingival tissues. Furthermore, bacterial invasion was strongly correlated with T-cell infiltration, which was associated with alveolar bone loss. Interestingly, both DSS and P. gingivalis shifted oral flora from Proteus-dominant community to Escherichia-dominant ones. Collectively, these findings suggest that a barrier-disrupting periodontal pathogen or chemical can induce periodontitis by facilitating bacterial invasion into tissues, leading to a subsequent inflammatory response. The association between compromised physical barriers and periodontitis was further supported by the reduction of ZO-1 expression in the periodontal lesions of patients with chronic periodontitis. Therefore, physical barriers may be a promising future target for the prevention and treatment of periodontitis.