ArticleClinical oral investigations2026
Increased TET3 expression associates with proinflammatory cytokines and reduced 5-hydroxymethylcytosine in periapical lesions.
Article in Clinical oral investigations, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo evaluate the association between apical periodontitis (AP) diagnosis and cytokine expression, exploring the mediating role of global 5-hydroxymethylcytosine (5-hmC) and the enzymes involved in DNA methylation and demethylation. MATERIALS AND
methodsA cross-sectional study included individuals with symptomatic AP (SAP; n = 18), asymptomatic AP (AAP; n = 19), and healthy periodontal ligament (HPL) (n = 11). mRNA levels of DNA methyltransferases (DNMT): DNMT1, DNMT3A; Ten-Eleven Translocation (TET) enzymes: TET2, TET3; and cytokines: IL-1β, and IL-6 were assessed by qRT-PCR in apical lesions and healthy periodontal ligament. Global %5-hmC was quantified by ELISA. Generalized structural equation models (GSEM) were used to evaluate the association between AP diagnosis and cytokine expression, considering %5-hmC and the expression of DNMT and TET genes as potential mediators, adjusted for age.
resultsSAP samples showed significantly higher DNMT1, DNMT3A, TET2, TET3, IL-1β, and IL-6 mRNA levels (p ≤ 0.05) and lower %5-hmC compared to HPL, but not when compared with AAP (p > 0.05). In AAP and SAP, DNMT3A, TET2, and TET3 correlated positively with IL-1β and IL-6, while in SAP, DNMT1, DNMT3A, and TET3 were inversely correlated with %5-hmC (p ≤ 0.05), an association not observed in AAP (p > 0.05). Furthermore, higher TET3 expression was associated with increased IL-1β and IL-6 mRNA levels (p ≤ 0.05) and with decreased global %5-hmC levels (p ≤ 0.05) in apical tissues.
conclusionsUpregulated TET3 expression is associated with proinflammatory responses and global methylation profiles in apical lesions, suggesting a potential role in the epigenetic regulation of AP. CLINICAL RELEVANCE: Epigenetic regulation of inflammatory cytokines may contribute to disease activity in periapical periodontitis.
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