Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2024; 16(4): 389-409
Published online Apr 26, 2024. doi: 10.4252/wjsc.v16.i4.389
Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis: Implications for bone health
Ling-Ling Wang, Zhan-Jin Lu, Shun-Kui Luo, Yun Li, Zhe Yang, Hong-Yun Lu
Ling-Ling Wang, Department of Gerontology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Zhan-Jin Lu, Shun-Kui Luo, Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Yun Li, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Zhe Yang, Hong-Yun Lu, Department of Endocrinology and Metabolism, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University, the First Hospital Affiliated with Medical College of Macao University of Science and Technology), Zhuhai 519000, Guangdong Province, China
Co-first authors: Ling-Ling Wang and Zhan-Jin Lu.
Author contributions: Wang LL and Lu ZJ contributed equally to this work; Wang LL and Lu HY are involved in study concept and design; Wang LL, Lu ZJ, Luo SK, Li Y, and Yang Z performed experiments; Luo SK, Li Y, and Yang Z provided material support and analytic tools; Wang LL, Lu ZJ, and Lu HY analyzed the data and wrote the manuscript; Lu HY had supervision of all study; and all authors read and approved the final manuscript.
Supported by Basic and Applied Basic Research Foundation of Guangdong Province, No. 2020A1515010123 and No. 2021A1515010695; and Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province, No. 2019A030317011.
Institutional animal care and use committee statement: The study was reviewed and approved by the Animal Care and Ethics Committee of the Fifth Affiliated Hospital of Sun Yat-sen University (Animal protocol number: 00054).
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: Hong-Yun Lu, MD, PhD, Chief Doctor, Department of Endocrinology and Metabolism, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University, the First Hospital Affiliated with Medical College of Macao University of Science and Technology), No. 79 Kangning Road, Zhuhai 519000, Guangdong Province, China. luhongyun@jnu.edu.cn
Received: November 9, 2023
Peer-review started: November 9, 2023
First decision: December 17, 2023
Revised: January 12, 2024
Accepted: February 21, 2024
Article in press: February 21, 2024
Published online: April 26, 2024
Processing time: 167 Days and 14.7 Hours
ARTICLE HIGHLIGHTS
Research background

Recently, several studies have demonstrated that hypoxia-inducible factor 2alpha (HIF-2α) is involved in bone mesenchymal stem cell (BMSC) osteogenic differentiation. However, the molecular mechanism involved remains unclear.

Research motivation

An exploration of osteoporosis (OP) treatments aimed at increasing bone formation is needed.

Research objectives

Research on the effects of HIF-2α on the osteogenic and adipogenic differentiation of BMSCs and hematopoietic function in the bone marrow niche.

Research methods

In vivo, we generated mice with BMSC-specific HIF-2α knockout and induced OP in these mice via three interventions: Bilateral ovariectomy, semilethal irradiation, and treatment with dexamethasone.

Research results

In vivo, the bone mass of KO mice was decreased compared with that of WT mice. In vitro, downregulation of HIF-2α inhibited osteogenesis and increased adipogenesis by suppressing the mechanistic target of rapamycin (mTOR) signaling pathway.

Research conclusions

In conclusion, through in vivo and in vitro experiments, we verified that inhibition of HIF-2α can decrease the osteogenic differentiation and increase the adipogenic differentiation of BMSCs by inhibiting the mTOR signaling pathway.

Research perspectives

In future research, as many patients with chronic kidney disease also have OP, we will verify whether the HIF-2α agonist roxadustat can successfully treat mice with OP induced via ovariectomy.