Zhou XC, Wang DX, Zhang CY, Yang YJ, Zhao RB, Liu SY, Ni GX. Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis. World J Orthop 2024; 15(4): 363-378 [PMID: 38680671 DOI: 10.5312/wjo.v15.i4.363]
Corresponding Author of This Article
Guo-Xin Ni, MD, PhD, Chief Doctor, Chief Physician, Professor, Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen 361003, Fujian Province, China. nigx@xmu.edu.cn
Research Domain of This Article
Orthopedics
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Xu-Chang Zhou, Dong-Xue Wang, Chun-Yu Zhang, Ruo-Bing Zhao, School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
Ya-Jing Yang, Department of Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
Sheng-Yao Liu, Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
Guo-Xin Ni, Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian Province, China
Co-first authors: Xu-Chang Zhou and Dong-Xue Wang.
Author contributions: Ni GX and Zhou XC designed and coordinated the study; Wang DX and Yang YJ performed the experiments, acquired and analyzed data; Zhao RB interpreted the data; Zhou XC and Liu SY acquired the Fund; Zhou XC and Wang DX wrote the manuscript; all authors approved the final version of the article.
Supported bythe Key Laboratory of Sports and Physical Health of the Ministry of Education (Beijing Sport University), the Fundamental Research Funds for the Central Universities, No. 20221021; the Guangzhou Science and Technology Plan Project, No. 202102020536; and the Plan on Enhancing Scientific Research in GMU.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Beijing Sport University (Approval Number: 2023026A).
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Guo-Xin Ni, MD, PhD, Chief Doctor, Chief Physician, Professor, Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen 361003, Fujian Province, China. nigx@xmu.edu.cn
Received: November 22, 2023 Peer-review started: November 22, 2023 First decision: January 24, 2024 Revised: February 4, 2024 Accepted: March 19, 2024 Article in press: March 19, 2024 Published online: April 18, 2024 Processing time: 144 Days and 0.3 Hours
ARTICLE HIGHLIGHTS
Research background
It is well known that exercise promotes bone growth and development. However, the underlying mechanisms by which exercise promotes bone formation are not fully understood.
Research motivation
Our previous findings suggest that the mechanosensitive lncRNA H19 is involved in the regulation of cartilage homeostasis. Therefore, we propose the hypothesis that mechanosensitive lncRNA H19 may be involved in mediating the process of exercise-promoted bone formation. This study will provide more theoretical basis for exercise promoting bone health.
Research objectives
The aim of this study was to investigate whether mechanosensitive lncRNA H19 could promote bone formation by targeting miR-149. This study reveals for the first time the potential regulatory role of the lncRNA H19/miR-149 axis in exercise-promoted bone formation, providing a scientific basis for the promotion of bone health by exercise.
Research methods
The potential role of lncRNA H19/miR-149 axis in exercise-promoted bone formation was fully validated in vivo and in vitro by RT-qPCR, WB, IF, IHC, and micro-CT combined with bioinformatics analysis.
Research results
In vivo, exercise could activate autophagy by promoting the expression of lncRNA H19 and inhibiting the expression of miR-149, thereby promoting bone formation. In vitro, knockdown of lncRNA H19 was able to inhibit autophagy by upregulating miR-149 expression, thereby inhibiting osteogenic differentiation of bone mesenchymal stem cells.
Research conclusions
Exercise can promote autophagy and bone formation through activation of the lncRNA H19/miR-149 axis.
Research perspectives
The potential role of the lncRNA H19/miR-149/autophagy axis in exercise-promoted bone formation was further validated by gain of function and loss of function in animal experiments.
