Neutrophil Extracellular Traps Aggravate Apical Periodontitis by Stimulating Osteoclast Formation

Autor(es)

Guilherme Neto, Joao Luiz ; Venturini, Lucas Gabriel Rodrigues ; Schneider, Ayda Henriques ; Taira, Thaise Mayumi ; Rodrigues, Leticia Fernanda Duf fles ; Veras, Favio Protasio ; Oliveira, Sicilia Rezende ; da Silva, Tarcilia Aparecida ; Cunha, Fernando Queiroz ; Fukada, Sandra Yasuyo

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ENDODONTICS; v. 49, n. 11, p. 8-pg., 2023-10-28.

Resumo

Introduction: Neutrophil extracellular traps (NETs) have been described as structures composed of DNA and proteins, such as elastase and myeloperoxidase, that are able to kill bacteria extracellularly. The aim of the present study was to evaluate the role of NETs in bone resorption observed in pulp infection-induced apical periodontitis in mice. Methods: Apical periodontitis was experimentally induced by exposing the dental pulp of the mandibular first molar of mice to the oral microenvironment. The expression of NETs was evaluated by immunofluorescence in mice and biopsies of apical periodontitis. Mice were treated with vehicle or DNase Ito degrade NETs, and the samples were collected after 7 days. The size of the apical lesion and the osteoclast number were determined in hematoxylin-eosin- and tartrate-resistant acid phosphatase-stained sections, respectively. Osteoclast differentiation and function markers were evaluated by quantitative polymerase chain reaction. The level of NETs in the serum was determined by the myeloperoxidase-DNA PicoGreen assay. Results: We first confirmed the presence of neutrophils and NETs at the site of the lesion in mice and in biopsies of patients with apical periodontitis. The treatment of mice with DNase I reduced the level of NETs in the serum and led to a reduction in apical lesion size and alveolar bone resorption. This effect was associated with a reduction of local inflammatory infiltrate and a reduced number of osteoclasts. We found that the increased expression of Acp5, Ctsk, and Rankl genes associated with osteoclast formation and function were abrogated by the absence of NETs. Conclusions: Our data highlight NETs as an important player in the pathogenesis of apical periodontitis with regard to the local inflammation and consequent bone resorption after pulp infection. (J Endod 2023;49:1514-1521.) (AU)

• Processo FAPESP: 19/08568-2 - Investigação do papel de vesículas extracelulares (VEs) na iniciação, propagação, regeneração e modelação da mineralização biológica
• Beneficiário: Pietro Ciancaglini
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/24073-8 - Papel de OGT em osteoclastos na perda óssea experimental
• Beneficiário: Sandra Yasuyo Fukada Alves
• Modalidade de apoio: Auxílio à Pesquisa - Regular