MiR-155 inhibition alleviates suppression of osteoblastic differentiation by high glucose and free fatty acids in human bone marrow stromal cells by upregulating SIRT1
| Autor: | Hongsheng Yang, Wen Zhao, Zongrui Cao, Bo Qu, He Jun, Zeng Zhimou, Xianming Pan, Zhanli Liu, Hua Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Stromal cell Physiology Clinical Biochemistry Down-Regulation Bone Marrow Cells Fatty Acids Nonesterified Bone and Bones miR-155 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Downregulation and upregulation Osteogenesis Physiology (medical) Humans biology Chemistry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Transfection RUNX2 MicroRNAs 030104 developmental biology Osteocalcin biology.protein Cancer research Alkaline phosphatase 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Pflügers Archiv - European Journal of Physiology. 472:473-480 |
| ISSN: | 1432-2013 0031-6768 |
| DOI: | 10.1007/s00424-020-02372-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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