DNA Methylation patterns of immune response-related genes in inflammatory external root resorption

Abstract Inflammatory external root resorption (IERR) is a pathological process defined by the progressive loss of dental hard tissue, dentin, and cementum, resulting from the combination of the loss of external root protective apparatus and root canal infection. It has been suggested that healing patterns after tooth replantation may be influenced by the genetic and immunological profiles of the patients. The purpose of the present investigation was to evaluate the DNA methylation patterns of 22 immune response-related genes in extracted human teeth presenting with IERR. Methylation assays were performed on samples of root fragments showing IERR and compared with healthy bone tissue collected during the surgical extraction of impacted teeth. The methylation patterns were quantified using EpiTect Methyl II Signature Human Cytokine Production PCR Array. The results revealed significantly higher hypermethylation of the FOXP3 gene promoter in IERR (65.95%) than in the bone group (23.43%) (p < 0.001). The ELANE gene was also highly methylated in the pooled IERR sample, although the difference was not statistically significant (p= 0.054). Our study suggests that the differential methylation patterns of immune response-related genes, such as FOXP3 and ELANE, may be involved in IERR modulation, and this could be related to the presence of root canal infection. However, further studies are needed to corroborate these findings to determine the functional relevance of these alterations and their role in the pathogenesis of IERR.

摘要 炎性外牙根吸收（Inflammatory external root resorption, IERR）是一类以牙齿硬组织、牙本质及牙骨质进行性丢失为特征的病理过程，其发病由牙根外部保护结构丧失与根管感染共同介导。已有研究表明，再植牙术后的愈合模式可能受患者遗传与免疫特征影响。本研究旨在评估22个免疫反应相关基因的DNA甲基化（DNA methylation）谱，样本取自确诊为IERR的拔除人牙。研究对表现为IERR的牙根碎片样本进行甲基化检测，并与阻生牙手术拔除时获取的健康骨组织样本进行对照。采用EpiTect Methyl II Signature Human Cytokine Production PCR Array对甲基化谱进行定量分析。结果显示，IERR组中FOXP3基因启动子的高甲基化率（65.95%）显著高于骨组织组（23.43%）（p < 0.001）。合并IERR样本中ELANE基因同样呈现高甲基化状态，但该差异未达到统计学显著性（p=0.054）。本研究提示，FOXP3与ELANE等免疫反应相关基因的差异性甲基化谱可能参与IERR的病理调控，该现象或与根管感染的存在相关。然而，仍需开展进一步研究以验证上述发现，明确此类甲基化改变的功能相关性及其在IERR发病机制中的作用。