miR-27a promotes osteogenic differentiation in glucocorticoid-treated human bone marrow mesenchymal stem cells by targeting PI3K
Abstract
MicroRNA-27a (miR-27a) modulates osteogenic differentiation (OD); however, the mechanism by which it influences osteoclastic activity in the glucocorticoid (GC)-elicited osteoporotic bone is still unclear. Bone marrow was obtained from the proximal femur of patients (n = 3) with a femoral neck fracture and those (n = 3) with steroid-related osteonecrosis of the femoral head (ONFH). GC was applied to an established ONFH cell model from human bone marrow mesenchymal stem cells (hBMSCs). The miR-27a expression profiles were found to be downregulated in ONFH samples and GC-induced hBMSCs using microarray analysis and real-time quantitative polymerase chain reaction, whereas the OD capacity of hBMSCs was significantly reduced in the GC group compared with the control group. Subsequent transfection of an miR-27a mimic in hBMSCs revealed that the OD capacity of cells was remarkably strengthened in the GC group compared with the miR-control group. Bioinformatics software (TargetScan) predicted that phosphoinositide 3-kinase (PI3K) might be a potential miR-27a target, which was indicated by dual-luciferase reporter assay. Compared with the control group, the GC group exhibited a significantly downregulated protein expression level of PI3K and its downstream protein kinase B (Akt) and mammalian target of rapamycin (mTOR) expression. Furthermore, administration of 10 μM 740 Y-P, a cell-permeable phosphopeptide activator of PI3K, to hBMSCs increased the expression of Akt and mTOR. Treatment with 740 Y-P reversed the effect of miR-27a on OD in hBMSCs. In conclusion, miR-27a is thought to relieve ONFH and the OD repression in GC-induced hBMSCs by targeting the PI3K/Akt/mTOR pathway.
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miRNAs carried by MSC-Exos specifically bind to mRNA in target cells, inhibiting post-transcriptional gene expression and influencing osteoblast proliferation, differentiation, and apoptosis.
“The miRNAs carried by MSC-Exos specifically bind to mRNA in target cells, inhibiting post-transcriptional gene expression and consequently influencing physiological functions, including osteoblast proliferation, differentiation, and apoptosis [[20], [21], [22], [23], [24]].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [22]
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- Authors
- Tang, J., Yu, H., Wang, Y., Duan, G., Wang, B., Li, W., & Zhu, Z.
- Affiliations
- Xuzhou Medical College (CN)
- Second Affiliated Hospital of Xuzhou Medical College (CN)
- Corresponding author
- Zhu, Ziqiang
- Venue
- Journal of Molecular Histology
- Published
- 2021-02-02
- Volume
- 52
- Issue
- 2
- Pages
- 279-288
- ISSN
- 1567-2379 (ISSN-L)
- 1567-2387
- OpenAlex
- W3129138861
- Cited by
- 16
- References
- 38
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2022: 4 · 2021: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Histology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone and Joint Diseases
- Keywords
- miR-27a, osteogenic differentiation, glucocorticoids, steroid-induced osteonecrosis of the femoral head, bone marrow mesenchymal stem cells, PI3K/AKT/mTOR pathway, microRNA target regulation, 740Y-P, osteoporosis, femoral neck fracture
- MeSH terms
- Cell Differentiation, Cell Survival, Cells, Cultured, Glucocorticoids, Humans, Blotting, Western, Phosphatidylinositol 3-Kinases, MicroRNAs, Mesenchymal Stem Cells
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