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MiR-155 inhibition alleviates suppression of osteoblastic differentiation by high glucose and free fatty acids in human bone marrow stromal cells by upregulating SIRT1

  • Molecular and cellular mechanisms of disease
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Diabetic osteoporosis is a severe and chronic complication of diabetes in the bone and joint system, and its pathogenesis is needed to be explored. In the present study, we examined the effect and underlying mechanism of miR-155 on osteogenic differentiation in human bone marrow–derived mesenchymal stem cells (hBMSCs) under high glucose and free fatty acids (HG-FFA) conditions. It was shown that miR-155 levels in hBMSCs increased corresponding to the time of exposure to HG-FFA treatment. MiR-155 expression was altered by transfecting miR-155 mimic or miR-155 inhibitor. HG-FFA exposure resulted in an obviously decrease in cell viability and alkaline phosphatase (ALP) activity, and downregulated the expressionof runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) in hBMSCs. Transfection of miR-155 mimic further exacerbated HG-FFA-induced inhibitory effect on osteogenic differentiation, and miR-155 inhibitor neutralized this inhibitory effect. Luciferase assays confirmed that SIRT1 was a direct target of miR-155 and can be negatively modulated by miR-155. Furthermore, SIRT1 siRNA partially counteracted miR-155 inhibitor–induced upregulation of SIRT1in HG-FFA-treated hBMSCs. SIRT1 siRNA also reversed the promotional effect of the miR-155 inhibitor on ALP activity and expression of the Runx2 and OCN proteins under HG-FFA conditions. In conclusion, the results suggest that miR-155 suppression promoted osteogenic differentiation of hBMSCs under HG-FFA conditions by targeting SIRT1. Inhibition of MiR-155 may provide a new therapeutic method for the prevention and treatment of diabetic osteoporosis.

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Author notes

  1. Bo Qu and Jun He contributed equally to this work.

Authors and Affiliations

  1. Orthopaedics, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Avenue, Xindu District, Chengdu, 610500, China

    Bo Qu, Jun He, Zhimou Zeng, Hongsheng Yang, Zhanli Liu, Zongrui Cao, Hua Yu, Wen Zhao & Xianming Pan

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  1. Bo Qu
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  2. Jun He
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Highlights

• MiR-155 was upregulated in HG-FFA conditions during osteogenic differentiation.

• MiR-155 inhibited the osteogenic differentiation of hBMSCs in HG-FFA conditions.

• SIRT1 was a direct target of miR-155.

• SIRT1 silence reversed miR-155 inhibitors-induced osteogenic differentiation in HG-FFA-treated hBMSCs.

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Qu, B., He, J., Zeng, Z. et al. MiR-155 inhibition alleviates suppression of osteoblastic differentiation by high glucose and free fatty acids in human bone marrow stromal cells by upregulating SIRT1. Pflugers Arch - Eur J Physiol 472, 473–480 (2020). https://doi.org/10.1007/s00424-020-02372-7

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  • DOI: https://doi.org/10.1007/s00424-020-02372-7

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