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Demethylase FTO promotes mechanical stress induced osteogenic differentiation of BMSCs with up-regulation of HIF-1α

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Abstract

Background

In orthodontics, mechanical stress plays an important role in the process of bone remodeling. Mechanical stress has an effect on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism remains to be studied. The aim of this study is to investigate the effects of demethyltransferase fat mass and obesity-associated (FTO) on osteogenic differentiation of BMSCs under mechanical stress condition.

Methods and results

The rat BMSCs were cultured in vitro, followed by flow cytometry to identify the cell surface antigens. Osteogenic differentiation of BMSCs was induced by mechanical stress by using the flexcell tension system for 6 h every day and 3 days in total. BMSCs were transfected by using plasmid for FTO knockdown. The expression level of FTO, hypoxia-inducible factor (HIF)-1α, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins (BMPs) and alkaline phosphatase (ALP) were measured by real-time qPCR, western blotting. ALP activity were determined by ALP staining assays. The expression of FTO and HIF-1α in BMSCs with mechanical stress were significantly higher than BMSCs without mechanical stress, also, the expression of osteogenic differentiation markers were higher in BMSCs with mechanical stress. Knockdown of FTO decreased expression of osteogenic differentiation marker and ALP activity in stretched BMSCs. In addition, the expression of HIF-1α was decreased after knocking down FTO.

Conclusions

FTO promotes the expression of HIF-1α and osteogenic differentiation under the condition of mechanical stress. This finding may facilitate the clinical application of orthodontics and the mechanism research of mechanical stress-induced osteogenesis.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Nature Science Foundation of China (Grant No. 11602122); Shandong Provincial Key Laboratory of Oral Tissue Regeneration Open Project Fund (Grant No. SDKQ202002); Shandong Province Medicine and Health Science and Technology Development Plan Project (Grant No. 202008030332).

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Authors and Affiliations

  1. Department of Stomatology, Qingdao Municipal Hospital, Qingdao, China

    Renhao Sun, Chunxi Zhang, Zhenggang Chen, Fang Yang, Fei Zeng & Qingyuan Guo

  2. School of Stomatology, Dalian Medical University, Dalian, China

    Renhao Sun & Wen Liu

  3. School of Stomatology, Qingdao University, Qingdao, China

    Yicong Liu & Qingyuan Guo

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  1. Renhao Sun
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  2. Chunxi Zhang
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  6. Fang Yang
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Contributions

RS, QG, ZC, and WL established the initial design of the study. RS, ZC, WL, and FZ performed the experiments and analyzed the data. RS, CZ, QG, and FY Participated in manuscript writing. FY, FZ, CZ, and QG confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

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Correspondence to Qingyuan Guo.

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The authors declare that there are no competing interests associated with the manuscript.

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The present study was approved by the Ethics Committee of Qingdao Municipal Hospital, Qingdao, China.

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Sun, R., Zhang, C., Liu, Y. et al. Demethylase FTO promotes mechanical stress induced osteogenic differentiation of BMSCs with up-regulation of HIF-1α. Mol Biol Rep 49, 2777–2784 (2022). https://doi.org/10.1007/s11033-021-07089-z

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