NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

Abstract

Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional microcomputed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

Trans‐cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans‐induced inflammation in THP‐1–derived macrophages via autophagy activation

“…C57BL/6 mice (male, 7 weeks old) were infected with Aa to induce experimental periodontitis with some modifications . To depress the resident oral flora, mice received sulfamethoxazole‐trimethoprim (2 g/L, sulfamethoxazole and trimethoprim) ad libitum in drinking water for 3 days.…”

TNF-α promotes expression of inflammatory factors by upregulating nicotinamide adenine dinucleotide phosphate oxidase-2 expression in human gingival fibroblasts

“…Some studies have shown that in the mouse model of periodontitis induced by Aggregatibacter actinomycetemcomitans ( Aa ), NOX-2 gene knockout mice have significantly reduced alveolar bone volume, increased inflammatory cell infiltration and the number of osteoclasts in periodontal tissues compared with the wild-type control group. 37 It has been reported that the level of IL-6 protein in central nervous system tissue was lower in NOX-2 knockout mice with experimental autoimmune encephalomyelitis. 38 In experimental atrial fibrillation mice, mRNA expressions of IL-6 and MCP-1 in atrial tissue of NOX-2 overexpressed mice showed no difference compared with wild-type control group.…”

Effects of mechanical strain on periodontal ligament fibroblasts in presence of Aggregatibacter actinomycetemcomitans lysate

“…NOS-2 thus appears to play a role in both compressive and tensile zones of the periodontal ligament during orthodontic tooth movement, as measured by the in vitro model presented here. The role of nitric oxide as an instrument of host response and its effects on bone metabolism have been controversially discussed by Bast et al [ 47 ]. Thus, both stimulatory-destructive and inhibitory-protective associations exist with increased bone loss after experimentally simulated periodontitis induced by infection with periodontal pathogens [ 48 , 49 ].…”

“…Thus, both stimulatory-destructive and inhibitory-protective associations exist with increased bone loss after experimentally simulated periodontitis induced by infection with periodontal pathogens [ 48 , 49 ]. Bone metabolism and inflammatory status can also be influenced by ROS [ 47 ]. Elevated levels of ROS are involved in the pathogenesis of most inflammatory diseases [ 50 , 51 ].…”