Impact of periodontal microRNAs associated with alveolar bone remodeling during orthodontic tooth movement: a randomized clinical trial

牙周微小RNA对正畸牙齿移动过程中牙槽骨改建的影响:一项随机临床试验

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作者:Alessandro Polizzi, Angela Alibrandi, Antonino Lo Giudice, Alfio Distefano, Laura Orlando, Amer M Analazi, Giuseppe Pizzo, Giovanni Li Volti, Gaetano Isola

Background

Micro-RNAs (miRNAs) have been reported to play an important role during orthodontic tooth movement (OTM) through the regulation of periodontal soft and hard tissue homeostasis and functions. The

Conclusions

In the present study, OTM significantly impacted the expression of the miRNAs analyzed, in both the tension and compression side of traction tooth at 3-month follow-up. High baseline miRNA-7a2-3p, -21-5p, -200b-3p, and lower miRNA-125b-2-3p, together with younger age and lower BOP, were significant predictors of OTM amount at 3-month follow-up.

Methods

Through a split-mouth design, 21 healthy patients (mean age 13.2 ± 1.8 years) were enrolled in the present study. Clinical parameters and gingival crevicular fluid (GCF) sampling were performed on both compression and tension sides of a random canine to be distalized (test groups) at baseline and at 1 h, 1 day, 1 month and at 3-month after OTM, while the contralateral canine served as a control group. miRNAs - 7a-3p, -7a-2-3p, -7a-5p, -21-3p, -21-5p, -100-3p, -100-5p, -125b-2-3p, -125b-5p, -200b-3p, and - 200b-5p expression was analyzed using a real-time quantitative polymerase chain reaction (RT-PCR). Data were analyzed to assess miRNAs change following OTM. Spearman test, two-way ANOVA and a multivariate regression model were established to evaluate the correlation among miRNAs and clinical parameters and to explore possible predictors of OTM amount at 3-month follow-up.

Results

At 3-month follow-up, there was an increase of miRNA-7a-2-3p, -21-5p, -100-5p, a decrease of miRNA-125b-5p, 200b-3p and - 200b-5p in the compression side and an increase of miRNA-7a-3p, 100-5p in the tension side (p < 0.05). The two-way ANOVA revealed that OTM determined, on the compression side, a significant upregulation on miRNA-7a-3p (p = 0.017), -7a-2-3p (p = 0.023), -21-5p (p = 0.007), -100-5p (p = 0.025) and a significant downregulation of miRNA-125b-2-3p (p = 0.019) and - 200b-5p (p = 0.017). The multivariate model highlighted that high baseline miRNA-7a2-3p (p = 0.025), -21-5p (p = 0.014), -200b-3p (p = 0.041), young age (p = 0.042), lower bleeding on probing (BOP) (p = 0.021) and miRNA-125b-2-3p (p = 0.021) levels were significant predictors of OTM at 3-month follow-up. Conclusions: In the present study, OTM significantly impacted the expression of the miRNAs analyzed, in both the tension and compression side of traction tooth at 3-month follow-up. High baseline miRNA-7a2-3p, -21-5p, -200b-3p, and lower miRNA-125b-2-3p, together with younger age and lower BOP, were significant predictors of OTM amount at 3-month follow-up.

Trial registration

ClinicalTrials.gov NCT06023433 (retrospectively registered).

文献解析

1. 文献背景信息

标题/作者/期刊/年份:  

    标题:Impact of periodontal microRNAs associated with alveolar bone remodeling during orthodontic tooth movement: a randomized clinical trial  

    作者:Alessandro Polizzi 等(意大利研究团队)  

    期刊:Journal of Translational Medicine(IF=6.100,2024年发表)  

 

• 权威性与时效性:发表于中高影响因子期刊,属近期研究,且为随机临床试验(RCT),证据等级较高。  

 

研究领域与背景:  

   领域:口腔正畸学与分子生物学交叉领域,聚焦牙周微小RNA(miRNA)在正畸牙齿移动(OTM)中对牙槽骨改建的调控作用。  

   研究现状:既往研究表明miRNA参与骨代谢调控,但OTM过程中特定miRNA的动态变化及其临床预测价值尚不明确。  

 

研究动机:  

  填补空白:首次通过RCT设计系统分析OTM中压力侧与张力侧miRNA表达谱变化,并探索其作为OTM效率预测标志物的潜力。  

 

2. 研究问题与假设

• 核心问题:哪些牙周miRNA在OTM过程中动态调控牙槽骨改建,并能否预测牙齿移动效率?  

• 假设:特定miRNA(如miR-21-5p、miR-200b-3p)的表达变化与OTM量显著相关,且基线水平可预测临床效果。  

 

3. 研究方法学与技术路线

实验设计:  

   分口设计(split-mouth):21名患者(平均13.2岁)随机选择一侧尖牙为实验组(远中移动),对侧为对照。  

   时间点:基线、1h、1天、1月、3月,采集龈沟液(GCF)并检测临床参数(如探诊出血BOP)。  

 

关键技术:  

   RT-qPCR检测11种miRNA(如miR-7a-3p、miR-21-5p等)。  

   统计分析:Spearman相关性检验、双向ANOVA、多元回归模型。  

 

创新方法:  

    首次在OTM中结合动态miRNA表达与临床参数建立预测模型。  

 

4. 结果与数据解析

主要发现:  

    表达变化:3个月时,压力侧miR-21-5p显著上调(p=0.007),miR-125b-2-3p下调(p=0.019);张力侧miR-7a-3p上调。  

    预测模型:基线高miR-7a-2-3p、-21-5p、-200b-3p及低miR-125b-2-3p,联合年轻年龄和低BOP,可显著预测3个月OTM量(p<0.05)。  

 

局限性:  

   样本量较小(n=21),且仅关注尖牙移动,结论外推需谨慎。  

 

5. 讨论与机制阐释

机制解释:  

   miR-21-5p可能通过促进破骨细胞分化加速骨吸收(压力侧),而miR-125b-2-3p下调可能解除对成骨抑制因子的调控。  

与既往研究对比:  

   支持miR-21在骨改建中的促吸收作用(与2019年Bone Research报道一致),但首次揭示其在OTM中的时间动态性。  

未解决问题:  

    miRNA调控的具体下游通路及是否适用于成人OTM需进一步研究。  

6. 创新点与学术贡献

理论创新:提出miRNA表达谱可作为OTM效率的生物标志物,推动个性化正畸治疗发展。  

 

实际价值:临床中通过基线miRNA检测预判治疗反应,优化矫治方案。  

 

技术推广:GCF miRNA检测方法可拓展至其他牙周疾病研究。  

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总结:该研究通过严谨的RCT设计,揭示了OTM中miRNA的动态调控规律,并建立了首个基于miRNA的临床预测模型,为口腔正畸的精准医疗提供了新思路。

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