TLR-2 gene methylation in peripheral blood monocytes from apical periodontitis individuals: A cross-sectional study
Aim Apical periodontitis (AP) is a chronic inflammatory disease arising from the contamination of the root canal system. Epigenetic regulation plays a pivotal role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges via toll-like receptors (TLRs). We aime...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 2025
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| In: |
International endodontic journal
Year: 2025, Volume: 58, Issue: 8, Pages: 1172-1183 |
| ISSN: | 1365-2591 |
| DOI: | 10.1111/iej.14255 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/iej.14255 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/iej.14255 
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| Author Notes: | María José Bordagaray, Alejandra Fernández, Elizabeth Pellegrini, Mauricio Garrido, Patricia Hernández, David González-Quintanilla, Gabriel Navia, Daniela Rehbein, Mauricio Baeza, Peter Gebicke-Haerter, Marcela Hernández |
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| 100 | 1 | |a Bordagaray, María José |e VerfasserIn |0 (DE-588)1375397923 |0 (DE-627)1935231162 |4 aut | |
| 245 | 1 | 0 | |a TLR-2 gene methylation in peripheral blood monocytes from apical periodontitis individuals |b A cross-sectional study |c María José Bordagaray, Alejandra Fernández, Elizabeth Pellegrini, Mauricio Garrido, Patricia Hernández, David González-Quintanilla, Gabriel Navia, Daniela Rehbein, Mauricio Baeza, Peter Gebicke-Haerter, Marcela Hernández |
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| 520 | |a Aim Apical periodontitis (AP) is a chronic inflammatory disease arising from the contamination of the root canal system. Epigenetic regulation plays a pivotal role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges via toll-like receptors (TLRs). We aimed to explore the relationship between the methylation and expression patterns of TLR-2 in peripheral blood monocytes of individuals with AP and controls. Methodology Cross-sectional study. Otherwise healthy individuals with AP (n = 25) and controls (n = 29) were recruited. Peripheral blood monocytes were isolated from blood samples by Ficoll gradient and negative immunoselection. DNA and RNA were extracted from monocytes. DNA was bisulfite-treated, amplified and sequenced to evaluate the global and cytosine-phosphate-guanine (CpG) single-site methylation pattern of the TLR-2 gene promoter. mRNA relative levels of TLR-2 were assessed by qPCR. The potential associations between AP, TLR-2 DNA methylation and TLR-2 gene expression were explored using generalized structural equation models (GSEM). Results TLR-2 expression was significantly upregulated in peripheral blood monocytes from individuals with AP compared to controls (p = 0.005). Though no differences were found in the global methylation pattern, CpG single sites from the TLR-2 gene were differentially methylated at positions −40 and +24 (p < 0.05). The methylated positions at −40 and −20 in TLR-2 were associated with TLR-2 transcriptional upregulation (p < 0.05). Further evaluation with GSEM analysis showed that AP promoted the methylation of the −40 CpG single site on the TLR-2 gene, which, in turn, upregulated TLR-2. Conversely, the methylation of the −20 CpG single site did not act as a mediator of TLR-2 transcription in AP. Conclusions AP diagnosis activates peripheral blood monocytes via −40 CpG single-site methylation, independently promoting TLR-2 expression. | ||
| 650 | 4 | |a DNA methylation | |
| 650 | 4 | |a monocytes | |
| 650 | 4 | |a periapical periodontitis | |
| 650 | 4 | |a toll-like receptor-2 | |
| 700 | 1 | |a Fernández, Alejandra |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pellegrini, Elizabeth |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garrido, Mauricio |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hernández, Patricia |e VerfasserIn |4 aut | |
| 700 | 1 | |a González-Quintanilla, David |e VerfasserIn |4 aut | |
| 700 | 1 | |a Navia, Gabriel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rehbein, Daniela |e VerfasserIn |4 aut | |
| 700 | 1 | |a Baeza, Mauricio |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Hernández, Marcela |e VerfasserIn |4 aut | |
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