Neutrophil Extracellular Traps Aggravate Apical Periodontitis by Stimulating Osteoclast Formation

Author(s)

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

• Document type: Journal article
• Source: JOURNAL OF ENDODONTICS; v. 49, n. 11, p. 8-pg., 2023-10-28.

Abstract

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)

• FAPESP's process: 19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization
• Grantee: Pietro Ciancaglini
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/24073-8 - The role of OGT of the osteoclast on experimental bone loss
• Grantee: Sandra Yasuyo Fukada Alves
• Support Opportunities: Regular Research Grants