Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy
Hai-Xiang Xiao, Lei Yu, Yu Xia, Kai Chen, Wen-Ming Li, Gao-Ran Ge, Wei Zhang, Qing Zhang, Hong-Tao Zhang, De-Chun Geng
Hai-Xiang Xiao, Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou 215006, Jiangsu Province, China
Hai-Xiang Xiao, Department of Orthopedics, Jingjiang People’s Hospital Affiliated to Yangzhou University, Jingjiang 214500, Jiangsu Province, China
Hai-Xiang Xiao, Lei Yu, Yu Xia, Wen-Ming Li, Gao-Ran Ge, Wei Zhang, De-Chun Geng, Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Kai Chen, Department of Orthopedics, Hai’an People’s Hospital, Hai’an 226600, Jiangsu Province, China
Qing Zhang, Department of Orthopedics, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an Second People’s Hospital, Xuzhou 223002, Jiangsu Province, China
Hong-Tao Zhang, Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Co-first authors: Hai-Xiang Xiao and Lei Yu.
Co-corresponding authors: Hong-Tao Zhang and De-Chun Geng.
Author contributions: Xiao HX, Yu L, and Xia Y contributed equally to this work; Xiao HX wrote the manuscript; Geng DC and Zhang HT contributed to the conception and design of the study and edited the original draft; Xiao HX, Yu L, and Xia Y performed the experiments and data validation; Chen K and Li WM proposed suggestions for manuscript revision; Ge GR, Zhang W, and Zhang Q provided technical help with the present experiment; Zhang HT and Geng DC contributed to the discussion of the data, funding acquisition and supervision; and all the authors have read and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82072425.
Institutional animal care and use committee statement: All animal experiments in this study were carried out with the approval of the Ethics Committee of the First Affiliated Hospital of Soochow University (ethics approval number: SUDA20221229A02).
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: De-Chun Geng, PhD, Professor, Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou 215006, Jiangsu Province, China.
szgengdc@suda.edu.cn
Received: November 20, 2023
Revised: March 1, 2024
Accepted: April 7, 2024
Published online: May 26, 2024
Processing time: 185 Days and 16 Hours
BACKGROUND
A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.
AIM
To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms.
METHODS
For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo, the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.
RESULTS
SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.
CONCLUSION
The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases.
Core Tip: Sinomenine (SIN) reduces the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway, inhibits mTOR activity, and increases autophagy of bone marrow mesenchymal stromal cells (BMSCs), thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice when used in vivo, thus providing support for the use of the traditional Chinese medicine SIN in the treatment of various types of osteoporosis, imbalances in bone homeostasis, and autophagy-related diseases.
