title: 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 (gp91phoxknockout [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 micro-computed 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 gp91phoxKO 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 gp91phoxKO mice. Only infected gp91phoxKO 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.
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Bast
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.|Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Kubis
authors.affiliation: Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Holtfreter
authors.affiliation: Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ribback
authors.affiliation: Institute for Biomedical Engineering, University of Rostock, Rostock, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Martin
authors.affiliation: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry, Newark, New Jersey, USA.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Schreiner
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.|Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Malte J
authors.initials: MJ
authors.lastname: Dominik
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Breitbach
authors.affiliation: Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dombrowski
authors.affiliation: Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kocher
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany ivo.steinmetz@medunigraz.at.|Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D058491:Bacterial Load; D015519:Bone Density; D004195:Disease Models, Animal; D060467:Disease Resistance; D005260:Female; D054884:Host-Pathogen Interactions; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010518:Periodontitis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*
chemical_list: D008562:Membrane Glycoproteins; D052247:Nitric Oxide Synthase Type II; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Aggregatibacter actinomycetemcomitans; NADPH oxidase; alveolar bone loss; bone mineral density; micro-computed tomography; periodontal disease