背景:正畸治疗错牙合期间的骨重建通常需要大约两到三年的长时间,这也可能导致一些并发症,如牙槽骨吸收或牙根吸收。低强度脉冲超声(LIPUS),非侵入性物理治疗,已被证明可以促进骨折愈合。据报道,LIPUS可以减少正畸治疗的持续时间;然而,LIPUS在正畸治疗过程中如何调节骨代谢仍不清楚。
目的:研究LIPUS对正畸牙齿移动(OTM)模型中骨改建的影响,并探讨其机制。
方法:建立OTM大鼠模型,通过显微计算机断层扫描和组织切片染色评估牙槽骨改建和牙齿移动速率。体外,通过定量逆转录-聚合酶链反应分离人骨髓间充质干细胞(hBMSCs)以检测其在压缩和LIPUS刺激下的成骨分化潜能,蛋白质印迹,碱性磷酸酶(ALP)染色,和茜素红染色。Yes相关蛋白(YAP1)的表达,肌动蛋白细胞骨架,应用或不应用YAP1小干扰RNA(siRNA),通过免疫荧光检测LaminA/C核骨架。
结果:力处理抑制了hBMSCs的成骨分化潜能;成骨标志物的表达,如1型胶原蛋白(COL1),runt相关转录因子2,ALP,和骨钙蛋白(OCN),decreased.LIPUS可以挽救hBMSCs的成骨分化,并增加成骨标志物的表达。机械上,层A/C的表达,F-肌动蛋白,强制治疗后YAP1下调,可以被LIPUS拯救。此外,LIPUS增强的hBMSCs成骨分化可以通过YAPsiRNA处理减弱。始终如一,LIPUS增加体内牙槽骨密度并减少垂直骨吸收。COL1、OCN、LIPUS部分挽救了牙槽骨受压侧的YAP1。
结论:LIPUS可通过调节细胞骨架-LaminA/C-YAP轴来加速牙齿移动和减少牙槽骨吸收,这可能是减少正畸治疗过程的有希望的策略。
BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.
OBJECTIVE: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms.
METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence.
RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.
CONCLUSIONS: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.