MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells

doi:10.4252/wjsc.v15.i10.979

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World Journal of Stem Cells

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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.

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

ARTICLE HIGHLIGHTS

Research background

Fracture healing is accompanied by obvious tissue hypoxia, it is worth exploring the effects of hypoxia on periosteal stem cells (PSCs) osteogenic differentiation. However, the underlying mechanisms needs to be clarified.

Research motivation

RUNX family transcription factor 2 (RUNX2) is a key regulator of osteogenic differentiation, and studies have found that RUNX2 has osteogenic activity in bone marrow mesenchymal stem cells, but its role in the osteogenic differentiation pathway of PSCs is still unclear.

Research objectives

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

Research methods

PSCs were extracted from 7-d-old C57BL/6J mice. Then, PSCs were stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were measured.

Research results

Hypoxia promotes PSC osteogenic differentiation. Also, miR-584-5p upregulation affects hypoxia-induced PSC osteogenic differentiation and RUNX2 axis was targeted by miR-584-59. The upregulation of RUNX2 specifically reversed the inhibitory effect of miR-584-5p overexpression on the hypoxia-induced PSC osteogenic differentiation.

Research conclusions

MiR-584-5p inhibited the hypoxia-induced PSC osteogenic differentiation via RUNX2.

Research perspectives

MiR-584-5p inhibits hypoxia-induced osteogenic differentiation of PSC through RUNX2, and PSC has good osteogenic/chondrogenic differentiation potential. These results indicate that miR-584-5p/RUNX2 axis may be a key target pathway for bone repair and regeneration.