Zheng Fu, Wu Tong, Wang Feifei, Tang Hongyi, Cui Xinyu, Liu Duo, Chen Peng, Fu Jiangfeng, Li Cuiying, Jiang Jiuhui
Department of Orthodontics, 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, China.
Center of Digital Dentistry, 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, China.
J Periodontal Res. 2025 Feb;60(2):189-199. doi: 10.1111/jre.13330. Epub 2024 Aug 2.
Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal inflammatory responses and impedes cementoblasts' mineralization capacity. Low-intensity pulsed ultrasound (LIPUS) shows potential in reducing OIIRR. However, the precise mechanisms through which LIPUS reduces OIIRR remain unclear. This study aimed to explore the effects and mechanisms of LIPUS on the mineralization of force-treated cementoblasts and its impact on OIIRR.
We established a rat OIIRR model and locally administered LIPUS stimulation for 7 and 14 days. We analyzed root resorption volume, osteoclast differentiation, and the expression of osteocalcin and yes-associated protein 1 (YAP1) using micro-computed tomography (micro-CT), hematoxylin and eosin, tartrate-resistant acid phosphatase, immunofluorescence and immunohistochemistry staining. In vitro, we applied compressive force and LIPUS to the immortalized mouse cementoblasts (OCCM30). We assessed mineralization using alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction, Western blotting and immunofluorescence staining.
In rats, LIPUS reduced OIIRR, as evidenced by micro-CT analysis and histological staining. In vitro, LIPUS enhanced mineralization of force-treated OCCM30 cells, as indicated by ALP and alizarin red staining, upregulated mRNA expression of mineralization-related genes, and increased protein expression of mineralization markers. Mechanistically, LIPUS activated YAP1 signaling via the cytoskeleton-Lamin A/C pathway, supported by immunofluorescence and Western blot analysis.
This study demonstrates that LIPUS promotes mineralization in force-treated cementoblasts and reduces OIIRR by activating YAP1 through the cytoskeletal-Lamin A/C signaling pathway. These findings provide fresh insights into how LIPUS benefits orthodontic treatment and suggest potential strategies for preventing and treating OIIRR.
正畸治疗通常会导致正畸诱导的炎性牙根吸收（OIIRR）。这种情况源于过大的正畸力，其会引发局部炎症反应并阻碍成牙骨质细胞的矿化能力。低强度脉冲超声（LIPUS）在减少OIIRR方面显示出潜力。然而，LIPUS减少OIIRR的确切机制仍不清楚。本研究旨在探讨LIPUS对受力处理的成牙骨质细胞矿化的影响及其机制，以及对OIIRR的影响。
我们建立了大鼠OIIRR模型，并局部给予LIPUS刺激7天和14天。我们使用显微计算机断层扫描（micro-CT）、苏木精和伊红染色、抗酒石酸酸性磷酸酶染色、免疫荧光和免疫组织化学染色分析牙根吸收体积、破骨细胞分化以及骨钙素和Yes相关蛋白1（YAP1）的表达。在体外，我们对永生化小鼠成牙骨质细胞（OCCM30）施加压缩力和LIPUS。我们使用碱性磷酸酶（ALP）染色、茜素红染色、实时定量聚合酶链反应、蛋白质免疫印迹和免疫荧光染色评估矿化情况。
在大鼠中，micro-CT分析和组织学染色表明LIPUS减少了OIIRR。在体外，ALP和茜素红染色表明LIPUS增强了受力处理的OCCM30细胞的矿化，上调了矿化相关基因的mRNA表达，并增加了矿化标志物的蛋白表达。从机制上讲，免疫荧光和蛋白质免疫印迹分析支持LIPUS通过细胞骨架-Lamin A/C途径激活YAP1信号。
本研究表明，LIPUS通过细胞骨架-Lamin A/C信号通路激活YAP1，促进受力处理的成牙骨质细胞矿化并减少OIIRR。这些发现为LIPUS如何有益于正畸治疗提供了新的见解，并提出了预防和治疗OIIRR的潜在策略。
