The interaction of miR-181a-5p and sirtuin 1 regulated human bone marrow mesenchymal stem cells differentiation and apoptosis

ABSTRACT

Osteoporosis (OP) characterizes a decrease in bone density and bone mass which leads to brittle fractures and serious damages to individuals. In recent years, various researches have proved that miRNAs act pivotally in the onset of bone-related diseases. In our research, we probed into the impact of miR-181a-5P on viability, differentiation, as well as apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). Our study reported that overexpressing miR-181a-5p considerably reduced the cell growth, whereas the miR-181a-5p inhibition showed opposite results. Furthermore, the hBMSCs apoptosis percentage was visually elevated or minimized after overexpressing or silencing miR-181a-5p, respectively. Our data also indicated that miR-181a-5p overexpression significantly inhibited ALP activity, and level of OPN, Runx2 and OCN at mRNA and protein level, whereas miR-181a-5p inhibition presented opposite results. In addition, based on luciferase reporter assay, sirtuin 1 (Sirt1) was confirmed as the target of miR-181a-5p in hBMSCs. Finally, Sirt1 overexpression significantly inhibited the impact of miR-181a-5p mimic on apoptosis and inhibited differentiation, while silencing Sirt1 eliminated the inhibitory effects of miR-181a-5p on apoptosis and promoted differentiation via PI3K/AKT pathway. In conclusion, this work revealed that miR-181a-5p could regulate hBMSCs apoptosis as well as differentiation via regulating Sirt1/PI3K/AKT signaling pathway.

Graphi Cal Abstract

KEYWORDS:

• Mir-181a-5p
• hBMSCs
• osteoporosis
• apoptosis

Highlights

1. MiR-181a-5p promoted hBMSCs apoptosis and inhibited the cell viability.

2. Inhibition of miR-181a-5p is associated with the increased hBMSCs differentiation.

3. MiR-181a-5p play vital inhibitory role in the Sirt1/PI3K/Akt signaling pathway to promote apoptosis and differentiation of hBMSCs

Acknowledgements

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Disclosure statement

No potential conflict of interest was reported by the author(s).

Declaration of Conflicts Interest

The author(s) declared no potential conflicts of interest regarding the research, authorship, and/or issuance of the paper.

Availability of data and materials

The data set applied and/or analyzed amidst existing studies are accessible to corresponding author on rational request.

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Authors’ contributions

HZ conceived as well as devised the research. HC together with XD analyzed the data. DD as well as SW contributed to literature review. HZ and YZ wrote the draft. HZ and YZ reviewed as well as redacted the piece of writing. All authors have read as well as ratified the final draft.

Additional information

Funding

The authors have no funding to report.