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正畸张力通过调节自噬促进成牙骨质细胞矿化。

Orthodontic tension promotes cementoblast mineralization by regulating autophagy.

作者信息

Zhao Yi, Yang Yuhui, Liu Hao, Wang Jiayi, Huang Yiping, Li Weiran

机构信息

Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.

National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China.

出版信息

J Dent Sci. 2024 Oct;19(4):2186-2195. doi: 10.1016/j.jds.2024.03.009. Epub 2024 Mar 19.

Abstract

BACKGROUND/PURPOSE: External root resorption is a main side effect of orthodontic treatment and is more likely to occur on the pression side than the tension side. To explore the potential protective mechanisms on the tension side, this study investigated the influence of mechanical tension on cementoblast mineralization and elucidated the role of autophagy in mediating this process.

MATERIALS AND METHODS

Mechanical tension was applied to cementoblasts using iStrain. The expression of mineralization-related and autophagy-related markers was detected by qRT-PCR, Western blot analysis, and immunofluorescence staining. RNA sequencing identified key regulators. Immunohistochemical staining assessed related markers expression in experiments.

RESULTS

Applying tension to cementoblasts increased mineralization-related gene expression in a force-dependent and time-dependent manner. The immunohistochemical staining result of experiments supported these findings, demonstrating elevated expression of mineralization markers under tension. Mechanical tension also enhanced autophagic activity in cementoblasts, which was demonstrated by the results of qRT-PCR, Western blot analysis, immunofluorescence staining, and experiments. Suppression of autophagy with chloroquine attenuated the mineralization of cementoblasts induced by tension stimulus. RNA-seq identified Postn as a key regulator, and the knockdown of Postn impaired the mechanical tension-promoted mineralization of cementoblasts.

CONCLUSION

This study proposed the tension-induced promotion in mineralization of cementoblasts and emphasized the mediating role of autophagy in this process. Postn, a mediator connecting autophagy and mineralization, was identified as a key regulator. These discoveries helped elucidate orthodontic-related microprocesses on tooth roots and offer potential targets for therapeutic interventions to prevent and restore external root resorption clinically.

摘要

背景/目的:牙根外吸收是正畸治疗的主要副作用,且在压力侧比张力侧更易发生。为探究张力侧的潜在保护机制,本研究调查了机械张力对成牙骨质细胞矿化的影响,并阐明了自噬在介导这一过程中的作用。

材料与方法

使用iStrain对成牙骨质细胞施加机械张力。通过qRT-PCR、蛋白质免疫印迹分析和免疫荧光染色检测矿化相关和自噬相关标志物的表达。RNA测序确定关键调节因子。免疫组织化学染色评估实验中相关标志物的表达。

结果

对成牙骨质细胞施加张力以力依赖和时间依赖的方式增加了矿化相关基因的表达。实验的免疫组织化学染色结果支持了这些发现,表明在张力作用下矿化标志物的表达升高。机械张力还增强了成牙骨质细胞中的自噬活性,qRT-PCR、蛋白质免疫印迹分析、免疫荧光染色和实验结果均证明了这一点。用氯喹抑制自噬减弱了张力刺激诱导的成牙骨质细胞矿化。RNA测序确定Postn为关键调节因子,敲低Postn会损害机械张力促进的成牙骨质细胞矿化。

结论

本研究提出了张力诱导的成牙骨质细胞矿化促进作用,并强调了自噬在此过程中的介导作用。Postn作为连接自噬和矿化的介质,被确定为关键调节因子。这些发现有助于阐明牙根上与正畸相关的微观过程,并为临床预防和修复牙根外吸收的治疗干预提供潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61f/11437326/85e10a23f8b4/gr1.jpg

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