Rolfes Florian, Heck Johannes, Riedel Isabelle, Bär Christian, Schmitz Boris
Dental Medical Center ALL DENTE, MVZ, Kamen, Germany.
Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, Hannover, Germany.
Sci Rep. 2025 Jun 3;15(1):19488. doi: 10.1038/s41598-025-01794-6.
This study aimed to identify functional microRNAs (miRNAs) and their respective targets as central regulatory factors of tooth movement during orthodontic treatment. Gingival crevicular fluid (GCF) of 24 adolescent patients (< 18 years) treated with a full-mouth multibracket appliance (MBA; Thermal Copper Nickel Titanium archwire) was analyzed for miRNAs-21, -29b, -34a, -126, -132, -146a, and -221. GCF samples were taken from the second premolar in either jaw using non-invasive sampling before, 7 days, 5 weeks, and 3 months after application of orthodontic force (8 samples per patient). Validated miRNA targets and regulated pathways were identified using the miRTarBase database (release 9.0) and Reactome (version 87). All analyzed miRNAs were consistently detected in the GCF (Ct value < 35) and a moderate to high correlation was found between samples taken from the mandible and maxilla before treatment (r = 0.42 to 0.71, all p ≤ 0.041). All miRNAs showed changes in their expression levels with orthodontic tooth movement compared to baseline (significant time effect, all p < 0.001). The general profile indicated an increase in miRNA expression in both jaws with time except for miR-21, which showed reduced levels one week after MBA application (p = 0.046). For miR-34, a significant interaction effect was observed (time × jaw, p = 0.0396) in that lower levels were found after five weeks and three months of treatment in the mandible compared to the maxilla. The medium to late treatment phase was characterized by an increase in miR-146 and miR-221. Gene signaling pathway analysis suggested regulation of cellular response to stress including hypoxia, matrix reorganization and vascular remodeling. Since the identified miRNA profile was linked to targets involved in the remodeling process of the alveolar supporting apparatus and alveolar bone, GCF-derived miRNAs may represent diagnostic biomarkers to monitor cellular processes during orthodontic tooth movement and potentially optimize individual treatment outcomes.
本研究旨在鉴定功能性微小RNA（miRNA）及其各自的靶标，作为正畸治疗期间牙齿移动的核心调节因子。分析了24例青少年患者（<18岁）使用全口多托槽矫治器（MBA；热铜镍钛弓丝）治疗后的龈沟液（GCF）中miRNA-21、-29b、-34a、-126、-132、-146a和-221的情况。在施加正畸力前、7天、5周和3个月后，使用无创采样从上下颌的第二前磨牙采集GCF样本（每位患者8个样本）。使用miRTarBase数据库（9.0版）和Reactome（87版）鉴定经过验证的miRNA靶标和调控途径。在GCF中始终检测到所有分析的miRNA（Ct值<35），并且在治疗前从下颌和上颌采集的样本之间发现了中度至高相关性（r = 0.42至0.71，所有p≤0.041）。与基线相比，所有miRNA在正畸牙齿移动时其表达水平均发生变化（显著的时间效应，所有p<0.001）。总体情况表明，随着时间的推移，上下颌中miRNA表达均增加，但miR-21除外，其在MBA应用后1周水平降低（p = 0.046）。对于miR-34，观察到显著的交互作用效应（时间×颌骨，p = 0.0396），即与上颌相比，下颌在治疗5周和3个月后水平较低。治疗的中晚期阶段的特征是miR-146和miR-221增加。基因信号通路分析表明，细胞对应激的反应受到调节，包括缺氧、基质重组和血管重塑。由于鉴定出的miRNA谱与参与牙槽支持装置和牙槽骨重塑过程的靶标相关，因此源自GCF的miRNA可能代表诊断生物标志物，以监测正畸牙齿移动期间的细胞过程，并可能优化个体治疗结果。
