TNF-a-TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis

Introduction: The aim of this study was to investigate the role of the proinflammatory axis TNF-a-TNFR1 in experimentally induced periapical inflammation and bone resorption in mice. Methods: 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 -a 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, his-topathologic, histomicrobiological, and histometric evaluation, tartrate-resistant acid phos-phatase 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 (a = 5%). Results: 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). Conclusions: Periapical inflammation and bone resorption were exacerbated in wild-type animals compared with TNFR1(-/-)mice, demon-strating that the TNF-a-TNFR1 signaling pathway mediated catabolic events in bone after root canal contamination. (J Endod 2023;49:1319-1328.)

Automated summary

This study investigated the role of the TNF-a-TNFR1 proinflammatory axis in periapical inflammation and bone resorption. The results showed that TNFR1(-/-) mice exhibited reduced inflammation and bone resorption compared to wild-type mice.