Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2024; 16(3): 267-286
Published online Mar 26, 2024. doi: 10.4252/wjsc.v16.i3.267
Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells
Tong Wu, Fu Zheng, Hong-Yi Tang, Hua-Zhi Li, Xin-Yu Cui, Shuai Ding, Duo Liu, Cui-Ying Li, Jiu-Hui Jiang, Rui-Li Yang
Tong Wu, Fu Zheng, Hong-Yi Tang, Hua-Zhi Li, Xin-Yu Cui, Shuai Ding, Duo Liu, Jiu-Hui Jiang, Rui-Li Yang, 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
Cui-Ying Li, 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
Co-first authors: Tong Wu and Fu Zheng.
Co-corresponding authors: Jiu-Hui Jiang and Rui-Li Yang.
Author contributions: Li CY, Jiang JH, and Yang RL were responsible for the study design and conduction; Jiang JH and Yang RL made equal contributions to the determination of study directions and the design of experimental methods, and they are the co-corresponding authors of this paper; Wu T and Zheng F contributed to the experimental implementation, data analysis, and manuscript writing equally; Tang HY, Li HZ, Cui XY, Ding S, and Liu D participated in some of the experiments; all authors approved the final version for submission.
Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2022YFA1105800; the National Natural Science Foundation of China, No. 81970940.
Institutional review board statement: The study was approved by Ethical Guidelines of Hospital of Stomatology, Peking University (Approval No. PKUSSIRB-202385020).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee for Animal Experiments at Peking University Health Science Center (IACUC protocol number No. LA2022288).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rui-Li Yang, PhD, Professor, 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, No. 22 Zhongguancun South Avenue, Beijing 100081, China. ruiliyangabc@163.com
Received: October 26, 2023
Peer-review started: October 26, 2023
First decision: December 17, 2023
Revised: December 30, 2023
Accepted: February 1, 2024
Article in press: February 1, 2024
Published online: March 26, 2024
ARTICLE HIGHLIGHTS
Research background

The bone remodeling during orthodontic treatment for malocclusion often requires a long duration, which also may lead to some complications such as alveolar bone resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing and reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.

Research motivation

How to shorten the orthodontic treatment duration and reduce the side effects caused by orthodontic treatment such as alveolar bone resorption has become a very important clinical problem. LIPUS, as a non-invasive physical therapy, has been reported to promote the fracture healing process, and may also play a good role in orthodontic treatment.

Research objectives

This study was to investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms.

Research methods

We established a rat model of OTM, 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 and to investigate the underlying mechanisms.

Research results

The force treatment inhibited the expression of osteogenesis markers and osteogenic differentiation potential of hBMSCs, which could be rescued by LIPUS treatment. Mechanically, the expression of LaminA/C, F-actin, and Yes-associated protein (YAP1) was downregulated after force application, which could be rescued by LIPUS treatment. Moreover, the osteogenic differentiation of MSCs increased by LIPUS treatment could be attenuated by YAP small interfering RNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of type 1 collagen, osteocalcin, and YAP1 on the compression side of the alveolar bone was partially rescued by the LIPUS treatment.

Research conclusions

By regulating the cytoskeleton-Lamin A/C-YAP axis, LIPUS can effectively accelerate tooth movement and reduce bone resorption. Therefore, LIPUS can be used as an effective auxiliary method for orthodontic treatment.

Research perspectives

These results may provide an adjunctive treatment strategy for orthodontic treatment and enrich the theoretical basis for LIPUS application.