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
Processing time: 151 Days and 0.6 Hours
Abstract
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.

AIM

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.

CONCLUSION

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.

Keywords: Low-intensity pulsed ultrasound; Bone resorption; Osteogenesis; Cytoskeleton-Lamin A/C-Yes-associated protein axis; Bone marrow mesenchymal stem cells; Orthodontic tooth movement

Core Tip: Low-intensity pulsed ultrasound can promote local alveolar bone remodeling and reduce vertical alveolar bone resorption and consequent gingival recession by regulating the osteogenic ability of bone marrow mesenchymal stem cells by upregulating the expression and nuclear translocation of Yes-associated protein decreased by mechanical stress via affecting the cytoskeleton and nuclear skeleton.