Deng Jie, Zhang Yu-Ning, Bai Ru-Shui, Yu Ting-Ting, Zhao Yi, Liu Hao, Zhang Yun-Fan, Xu Tian-Min, Han Bing
Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory for Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Najing, China.
Prog Orthod. 2025 Jan 2;26(1):2. doi: 10.1186/s40510-024-00548-w.
Yes-associated protein (YAP) is a crucial mechanosensor involved in mechanotransduction, but its role in regulating mechanical force-induced bone remodeling during orthodontic tooth movement (OTM) is unclear. This study aims to elucidate the relationship between mechanotransduction and mechanical force-induced alveolar bone remodeling during OTM.
Our study confirms an asynchronous (temporal and spatial sequence) remodeling pattern of the alveolar bone under mechanical force during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone, whereas no significant presence of osteoblasts in the alveolar bone at the early stages of bone remodeling. Specifically, applying different force magnitudes (10, 25, 50, 100 g) to rats' 1st molars affected OTM distance. Force-induced alveolar bone remodeling was characterized by osteoclastogenesis and YAP activation at compressive/tensile sites on day 1 of OTM. Notably, 25 g force triggered peak YAP expression and osteoclastic activity early on. Time-course analysis revealed two YAP activity peaks on day1 and 14, contrasting with one peak of type I collagen expression on day14. In addition, RNA-sequencing highlighted increased nuclear factor kappa B (NF-κB) signaling, mineral absorption, and osteoclast differentiation at day-1 and 3. Moreover, gene expression analysis showed similar trends for NF-κB p65, YAP1, and TEA domain 1 (TEAD1) during this time. Furthermore, experiments on osteoclast cultures indicated YAP activation via large tumor suppressor (LATS) and TEAD under mechanical stimuli (compression/tension), promoting osteoclastogenesis by regulating NF-κB p65 and receptor activator of NF-κB (RANK). Inhibiting YAP with verteporfin delayed OTM by impairing force-induced osteoclastic activities in vivo and ex-vivo.
We propose that YAP mediates alveolar bone remodeling through NF-κB p65-induced osteoclastogenesis in an asynchronous remodeling pattern during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone at early stages of bone remodeling, offering evidence for orthodontists as a reference.
Yes相关蛋白（YAP）是一种参与机械转导的关键机械传感器，但其在正畸牙齿移动（OTM）过程中调节机械力诱导的骨重塑中的作用尚不清楚。本研究旨在阐明OTM过程中机械转导与机械力诱导的牙槽骨重塑之间的关系。
我们的研究证实了OTM过程中牙槽骨在机械力作用下的异步（时间和空间序列）重塑模式。压缩和拉伸均激活破骨细胞向牙槽骨募集，而在骨重塑早期牙槽骨中未发现明显的成骨细胞。具体而言，对大鼠第一磨牙施加不同大小的力（10、25、50、100克）会影响OTM距离。力诱导的牙槽骨重塑在OTM第1天的压缩/拉伸部位以破骨细胞生成和YAP激活为特征。值得注意的是，25克力在早期触发了YAP表达和破骨细胞活性的峰值。时间进程分析显示在第1天和第14天有两个YAP活性峰值，而I型胶原蛋白表达在第14天有一个峰值。此外，RNA测序突出显示在第1天和第3天核因子κB（NF-κB）信号传导、矿物质吸收和破骨细胞分化增加。此外，基因表达分析显示在此期间NF-κB p65、YAP1和TEA结构域1（TEAD1）有相似的趋势。此外，破骨细胞培养实验表明在机械刺激（压缩/拉伸）下YAP通过大肿瘤抑制因子（LATS）和TEAD激活，通过调节NF-κB p65和NF-κB受体激活剂（RANK）促进破骨细胞生成。用维替泊芬抑制YAP会通过损害体内和体外力诱导的破骨细胞活性而延迟OTM。
我们提出YAP在OTM的异步重塑模式中通过NF-κB p65诱导的破骨细胞生成介导牙槽骨重塑。压缩和拉伸在骨重塑早期均激活破骨细胞向牙槽骨募集，为正畸医生提供了参考依据。
