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High glucose mediates apoptosis and osteogenesis of MSCs via downregulation of AKT-Sirt1-TWIST

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Abstract

Background

Mesenchymal stem cells have been widely used in the treatment of diabetes mellitus. However, hyperglycemia associated with DM promotes cell apoptosis and affects osteogenic differentiation of MSCs in varying degrees, leading to osteoporosis in DM patients. Therefore, in this paper, the effect of high glucose on apoptosis and osteogenesis of MSCs was investigated and underlying mechanism was further determined.

Methods and results

Intracellular ROS levels were determined using probe DCFH-DA. MMP was detected using JC-1 staining. Cell apoptosis was detected using Annexin V-FITC/PI and Flow Cytometer. The expression of genes and protein was detected by qRT-PCR and Western blot respectively. The results showed high glucose induced MSC apoptosis but promoted its osteogenesis. Western blot analysis revealed that high glucose downregulated AKT-Sirt1-TWIST pathway. Activation of Sirt1 via SRT1720 increased TWIST expression, alleviated MSC apoptosis and promoted osteogenesis of MSCs. TWIST knockdown studies demonstrated that inhibition of TWIST intensified high glucose-induced apoptosis but promoted osteogenesis differentiation of MSCs. TWIST is likely to be a new regulator for cross talk between Sirt1 and its downstream targets.

Conclusion

Our data demonstrates that high glucose induces MSC apoptosis and enhances osteogenesis differentiation via downregulation of AKT-Sirt1-TWIST.

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Data availability

All data generated or analyzed during this study are included in this manuscript.

Code availability

Not applicable.

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Funding

This work was supported by grants from the National Key Research and Development Program of China (Grant No. 2018YFC1105800), the National Natural Science Foundation of China (Grant No. 81671841), and the Fundamental Research Funds for the Central Universities (Grant No. 22221818014).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Wenxia Ren, Miaomiao Chai, Mingli Jiang, Yan Zhou & Wensong Tan

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  1. Wenxia Ren
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  2. Miaomiao Chai
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  3. Mingli Jiang
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  4. Yan Zhou
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Contributions

Conceptualization: WR; Data curation: WR; Methodology: WR; Writing-Original draft preparation: WR; Writing-Reviewing and Editing: WR, MC, MJ, YZ; Supervision; YZ,WT. The manuscript is approved by all authors. The order of authors listed in the manuscript has been approved by all authors.

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Correspondence to Yan Zhou.

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Not Applicable. This article does not contain any studies with human participants or animals performed by any of the authors.

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Ren, W., Chai, M., Jiang, M. et al. High glucose mediates apoptosis and osteogenesis of MSCs via downregulation of AKT-Sirt1-TWIST. Mol Biol Rep 49, 2723–2733 (2022). https://doi.org/10.1007/s11033-021-07082-6

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  • DOI: https://doi.org/10.1007/s11033-021-07082-6

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