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The aim of this study was to investigate the role of the proinflammatory axis TNF-α-TNFR1 in experimentally induced periapical inflammation and bone resorption in mice. After receiving Ethics Committee Approval (2019.1.139.58.0), experimental apical periodontitis was induced by means of inoculating oral microorganisms into the root canals of molars of mice. Genetically deficient tumor necrosis factor-α receptor-1 mice (TNFR1-/-; n = 50) response was compared with that of C57Bl6 wild-type mice (wild-type; n = 50) after 7, 14, 28, and 42 days. The analyses performed were micro-computed tomographic, histopathologic, histomicrobiological, and histometric evaluation, tartrate-resistant acid phosphatase staining, immunohistochemistry, and quantitative reverse transcriptase polymerase chain reaction. Data were analyzed by using one-way analysis of variance, followed by Tukey or Bonferroni tests (α = 5%). TNFR1-/- mice exhibited lower recruitment of neutrophils at 14, 28, and 42 days (P < .05), which resulted in reduced area and volume of apical periodontitis at 42 days (P < .05). The number of osteoclasts was also lower in TNFR1-/- animals at 14 and 42 days (P < .01), along with reduced synthesis of CTSK, MMP-9, and COX-2. Expression of RANKL, but not OPG, was reduced at 14 and 42 days (P < .001). The highest RANKL expression over OPG (ratio > 1) was found in wild-type animals at 7 (P < .0001) and 42 days (P < .001). Periapical inflammation and bone resorption were exacerbated in wild-type animals compared with TNFR1-/- mice, demonstrating that the TNF-α-TNFR1 signaling pathway mediated catabolic events in bone after root canal contamination. Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Citation

Luciano Aparecido Almeida-Junior, Marcio Santos de Carvalho, Lana Kei Yamamoto Almeida, Alice Corrêa Silva-Sousa, Manoel Damião Sousa-Neto, Raquel Assed Bezerra Silva, Léa Assed Bezerra Silva, Francisco Wanderley Garcia Paula-Silva. TNF-α-TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis. Journal of endodontics. 2023 Jul 26


PMID: 37499863

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