Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2023; 15(10): 979-988
Published online Oct 26, 2023. doi: 10.4252/wjsc.v15.i10.979
MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells
Jia-Jia Lu, Xiao-Jian Shi, Qiang Fu, Yong-Chuan Li, Lei Zhu, Nan Lu
Jia-Jia Lu, Yong-Chuan Li, Nan Lu, Department of Orthopedic Trauma Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200001, China
Jia-Jia Lu, Qiang Fu, Lei Zhu, Department of Orthopedic Trauma Surgery, Shanghai Changzheng Hospital, Shanghai 200001, China
Xiao-Jian Shi, Department of Orthopedic Trauma, Haimen People’s Hospital of Jiangsu Province, Nantong 226100, Jiangsu Province, China
Co-corresponding authors: Lei Zhu and Nan Lu.
Author contributions: Lu JJ, Shi XJ, Fu Q, Li YC, and Zhu L contributed equally to this work. Lu JJ, Shi XJ, Fu Q, Li YC, and Zhu L designed the research study, contributed new reagents and analytic tools, analyzed the data, and wrote the manuscript; Lu JJ, Shi XJ, Fu Q, Li YC, Zhu L, and Lu N performed the research; and all authors have read and approve the final manuscript. First, the research was performed as a collaborative effort, and the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper’s quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers’ understanding by offering various expert perspectives. Third, Zhu L and Lu N contributed efforts of equal substance throughout the research process. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. In summary, we believe that designating Zhu L and Lu N as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team’s collaborative spirit, equal contributions, and diversity.
Supported by Sailing Program of Naval Medical University, Program of Shanghai Hongkou District Health Commission, No. 2202-27; and Special Funds for Activating Scientific Research of Shanghai Fourth People’s Hospital, No. sykyqd05801.
Institutional animal care and use committee statement: All animal experiments were performed in accordance with the guidelines of the Committee on the Ethics of Animal Experiments of Tongji University, No. TJBJI2523101.
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: Nan Lu, PhD, Doctor, Department of Orthopedic Trauma Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, No. 1279 Sanmen Road, Hongkou District, Shanghai 200001, China. nanlu_1981@163.com
Received: July 27, 2023
Peer-review started: July 27, 2023
First decision: August 15, 2023
Revised: September 23, 2023
Accepted: October 17, 2023
Article in press: October 17, 2023
Published online: October 26, 2023
Processing time: 90 Days and 22.8 Hours
Abstract
BACKGROUND

The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear.

AIM

To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs.

METHODS

In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.

RESULTS

Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p, antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.

CONCLUSION

Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

Keywords: Periosteal stem cell; Osteogenic differentiation; RUNX family transcription factor 2; MiroRNA-584-5p

Core Tip: This study simulated the hypoxic environment of periosteal stem cells (PSCs) during fracture and examined the related cellular responses to the hypoxia-induced PSC osteogenic differentiation. Importantly, the microRNA-584-5p/RUNX family transcription factor 2 axis was determined to be one of the regulating mechanisms for the hypoxia-induced PSC osteogenic differentiations.