MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells
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. To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5...
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| Published in | World journal of stem cells Vol. 15; no. 10; pp. 979 - 988 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Baishideng Publishing Group Inc
26.10.2023
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| Subjects | |
| Online Access | Get full text |
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| Summary: | 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.
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.
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.
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.
Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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 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. 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. Co-corresponding authors: Lei Zhu and Nan Lu. |
| ISSN: | 1948-0210 1948-0210 |
| DOI: | 10.4252/wjsc.v15.i10.979 |