MicroRNA⁃21调控破骨和成骨分化作用在正畸治疗中的研究进展

Research progress on microRNA⁃21 in regulating osteoclast and osteogenic differentiation in orthodontic treat⁃ment

在正畸矫治过程中,牙槽骨塑建与矫治器施加的机械应力的平衡是正畸牙有效移动的关键。牙槽骨塑建涉及众多调控因素,microRNAs(miRNAs)作为转录后调控因子,对骨塑建的发生起着重要的作用。作为miRNAs家族中的一个重要成员,研究证明miRNA⁃21可促进牙周膜干细胞向成骨细胞分化,同时作为破骨细胞生成的调节剂和破骨细胞分化的启动子,miRNA⁃21在维持骨平衡、防止骨吸收中发挥重要作用。文献复习结果表明,miRNA⁃21通过调控程序性细胞死亡蛋白4(programmed cell death 4,PDCD4)、蛋白酪氨酸磷酸酶(phosphate and tension homology deleted on chromsome ten,PTEN)、核因子κB受体活化因子配体(receptor acti⁃vator of nuclear factor⁃κB ligand,RANKL)和骨骼保护因子(osteoprotegerin,OPG)等因子调节破骨细胞功能,促进体内骨吸收。miRNA⁃21在正畸牙移动过程中对外界机械应力高度敏感,在施加正畸力后,miRNA⁃21可促进破骨细胞生成从而加快正畸移动速度;通过靶向调节牙周膜相关蛋白1(periodontal ligament associated pro⁃tein⁃1,PLAP⁃1)在牙齿移动后期调控牙周膜重塑,改善牙齿移动的潜能。另外,miRNA⁃21在牙周炎性微环境下同时介导正畸牙移动(orthodontic tooth movement,OTM)和牙槽骨重塑;在缺氧环境中可上调牙周膜干细胞(periodontal ligament stem cells,PDLCs)中的缺氧诱导因子⁃1α(Hypoxia⁃inducible factor⁃1α,HIF⁃1α)的表达;促进成骨标志物如骨桥蛋白(osteopontin,OPN)、骨钙素(Osteocalcin,OCN)和碱性磷酸酶(alkaline phosphatase,ALP)与Runt相关转录因子2(runt⁃related transcription factor 2,Runx2)的表达;在正畸牙移动过程中促进成骨分化。

In the process of orthodontic treatment,the balance between the modeling of alveolar bone and the me⁃chanical stress exerted by the appliance is key to the effective movement of orthodontic teeth.Alveolar bone modeling involves many regulatory factors,and microRNAs(miRNAs),as posttranscriptional regulatory factors,play an important role in the occurrence of bone modeling.As an important member of the miRNA family,miRNA⁃21 promotes the differentiation of periodontal ligament stem cells into osteoblasts and plays an important role in maintaining bone balance and preventing bone resorption as a regulator of osteoclast formation and a promoter of osteoclast differentiation.A literature review showed that miRNA⁃21 can regulate osteoclast function and promote bone resorption through programmed cell death 4(PDCD4),phosphate and tension homology deleted on chromosome ten(PTEN),receptor activator of nuclear fac⁃tor⁃κB ligand(RANKL)and osteoprotegerin(OPG).MiRNA⁃21 is highly sensitive to external mechanical stress in the process of orthodontic tooth movement.After orthodontic force is applied,miRNA⁃21 can promote osteoclast formation and accelerate orthodontic movement;through targeted regulation of periodontal ligament associated protein⁃1(PLAP⁃1),it can regulate periodontal ligament remodeling in the late stage of tooth movement and improve the potential of tooth movement.In addition,miRNA⁃21 mediates orthodontic tooth movement(OTM)and alveolar bone remodeling in the periodontal inflammatory microenvironment.miRNA⁃21 can upregulate the expression of hypoxia⁃inducible factor⁃1α(HIF⁃1α)in periodontal ligament stem cells in a hypoxic environment.It can promote the expression of osteogenic mark⁃ers,such as osteopontin(OPN),osteocalcin(OCN),alkaline phosphatase(ALP)and runt⁃related transcription factor 2(Runx2),and promote osteogenic differentiation during orthodontic tooth movement.