title: Induction of bone loss by pathobiont-mediated Nod1 signaling in the oral cavity.
abstract: Periodontitis is a common disease that is characterized by resorption of the alveolar bone and mediated by commensal bacteria that trigger host immune responses and bone destruction through unidentified mechanisms. We report that Nod1, an innate intracellular host receptor for bacterial peptidoglycan-related molecules, is critical for commensal-induced periodontitis in a mouse model. Mice lacking Nod1 exhibit reduced bone resorption as well as impaired recruitment of neutrophils to gingival tissues and osteoclasts to the alveolar bone, which mediate tissue and bone destruction. Further analysis showed that accumulation of a Nod1-stimulating commensal bacterium, NI1060, at gingival sites was sufficient to induce neutrophil recruitment and bone resorption. Genomic sequencing revealed that NI1060 is a mouse-specific bacterium that is related to bacteria associated with the development of aggressive periodontitis in humans. These findings provide insight into commensal-host interactions contributing to periodontitis and identify a potential target for preventing this common oral disease.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Yizu
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Structural Biology, Flemish Institute for Biotechnology, 1050 Brussels, Belgium.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Darzi
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tawaratsumida
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Julie T
authors.initials: JT
authors.lastname: Marchesan
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Moon
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
authors.affiliation: Department of Structural Biology, Flemish Institute for Biotechnology, 1050 Brussels, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: ino@umich.edu.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
mesh_terms: D016301:Alveolar Bone Loss / Q000473:pathology*; D000818:Animals; D001419:Bacteria / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D051379:Mice; D009055:Mouth / Q000382:microbiology*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D010518:Periodontitis / Q000150:complications / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse