Wu Tong, Zheng Fu, Tang Hong-Yi, Li Hua-Zhi, Cui Xin-Yu, Ding Shuai, Liu Duo, Li Cui-Ying, Jiang Jiu-Hui, Yang Rui-Li
Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
Department of Central Laboratory, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
World J Stem Cells. 2024 Mar 26;16(3):267-286. doi: 10.4252/wjsc.v16.i3.267.
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.
To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms.
A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated micro-computed tomography and staining of tissue sections. , 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 immunofluorescence.
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 The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.
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.
错牙合畸形正畸治疗期间的骨重塑通常需要大约两到三年的较长时间，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）作为一种非侵入性物理治疗方法，已被证明可促进骨折愈合。也有报道称LIPUS可缩短正畸治疗时间；然而，LIPUS在正畸治疗过程中如何调节骨代谢仍不清楚。
研究LIPUS对正畸牙移动（OTM）模型中骨重塑的影响，并探讨其潜在机制。
建立大鼠OTM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重塑和牙齿移动速率。此外，分离人骨髓间充质干细胞（hBMSCs），通过定量逆转录-聚合酶链反应、蛋白质免疫印迹法、碱性磷酸酶（ALP）染色和茜素红染色检测其在压缩和LIPUS刺激下的成骨分化潜能。在应用或不应用Yes相关蛋白（YAP1）小干扰RNA（siRNA）的情况下，通过免疫荧光检测YAP1、肌动蛋白细胞骨架和核纤层蛋白A/C核骨架的表达。
力作用处理抑制了hBMSCs的成骨分化潜能；此外，成骨标志物如Ⅰ型胶原（COL1）、 runt相关转录因子2、ALP和骨钙素（OCN）的表达降低。LIPUS可挽救hBMSCs的成骨分化，增加被力抑制的成骨标志物的表达。在机制上，力作用处理后核纤层蛋白A/C、F-肌动蛋白和YAP1的表达下调，而LIPUS可使其恢复。此外，YAP siRNA处理可减弱LIPUS增加的hBMSCs成骨分化。同样，LIPUS增加了牙槽骨密度并减少了垂直骨吸收，LIPUS部分挽救了牙槽骨压缩侧COL1、OCN和YAP1表达的降低。
LIPUS可通过调节细胞骨架-核纤层蛋白A/C-YAP轴加速牙齿移动并减少牙槽骨吸收，这可能是缩短正畸治疗过程的一种有前景的策略。
