Author(s): Souza, Joao A.C. [UNESP] ; Medeiros, Marcell C. [UNESP] ; Rocha, Fernanda R.G. [UNESP] ; De Aquino, Sabrina G. [UNESP] ; Ávila-Campos, Mario J. ; Spolidorio, Luis C. [UNESP] ; Zamboni, Dario S. ; Graves, Dana T. ; Rossa, Carlos [UNESP]
Date: 2018
Persistent ID: http://hdl.handle.net/11449/173651
Origin: Oasisbr
Subject(s): Bone resorption; inflammation; innate immunity; macrophages; NOD2 signaling adaptor protein
Made available in DSpace on 2018-12-11T17:07:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-11-01
National Institute of Dental and Craniofacial Research
NOD2 is a member of the NLR family of proteins that participate in the activation of the innate immune response. RIP2 is a downstream kinase activated by both NOD1 and NOD2. There is scarcity of information regarding the relevance of NOD2 in periodontitis, a chronic inflammatory condition characterized by inflammatory bone resorption. We used NOD2-KO and RIP2-KO mice in a model of microbial-induced periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans was injected in the gingival tissues three times/wk for 4 wk. Bone resorption was assessed by μCT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. In vitro studies using primary macrophages assessed the response macrophages using qPCR-based array and multi-ligand ELISA. Bone resorption and osteoclastogenesis were significantly reduced in NOD2-KO mice. Severity of inflammation was not affected. qPCR-focused arrays and multi-ligand ELISA showed that expression of pro-inflammatory mediators was reduced in NOD2- and RIP2-deficient cells. RANKL-induced osteoclastogenesis was impaired in NOD2- and RIP2-deficient macrophages. We conclude that NOD2 is important for osteoclast differentiation and inflammatory bone resorption in vivo and also for the macrophage response to Gram-negative bacteria.
Department of Diagnosis and Surgery School of Dentistry at Araraquara Univ Estadual Paulista (UNESP), Rua Humaita, 1680, Centro
Department of Microbiology Institute of Biomedical Sciences-Univ de Sao Paulo (USP)
Department of Physiology and Pathology School of Dentistry at Araraquara-Univ Estadual Paulista (UNESP)
Department of Cell Molecular Biology and Biopathogenic Agents School of Medicine at Ribeirao Preto-Univ de Sao Paulo (USP)
Department of Periodontics School of Dental Medicine-University of Pennsylvania
Department of Diagnosis and Surgery School of Dentistry at Araraquara Univ Estadual Paulista (UNESP), Rua Humaita, 1680, Centro
Department of Physiology and Pathology School of Dentistry at Araraquara-Univ Estadual Paulista (UNESP)
National Institute of Dental and Craniofacial Research: R01DE017732
National Institute of Dental and Craniofacial Research: R01DE021921
