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LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway

  • Authors:
    • Yingxing Xu
    • Yaping Jiang
    • Yingzhen Wang
    • Zhiping Zhao
    • Tao Li
  • View Affiliations / Copyright

    Affiliations: Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Medical Department of Qingdao University, Qingdao, Shandong 266071, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 171-182
    |
    Published online on: November 11, 2020
       https://doi.org/10.3892/ijmm.2020.4788
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Abstract

The inhibition of the proliferation and apoptosis of bone marrow‑derived mesenchymal stem cells (BMSCs) triggered by the excessive use of glucocorticoids, is considered a potential mechanism for the pathogenesis of steroid‑induced osteonecrosis of the femoral head (SONFH). Long non‑coding RNAs (lncRNAs) have been proven to influence the proliferation, apoptosis and differentiation of BMSCs by regulating the expression of critical genes. A previous microarray analysis by the authors confirmed the significant downregulation of LINC00473 in human BMSCs (hBMSCs) from patients with SONFH. However, the underlying role and molecular mechanisms of LINC00473 on dexamethasone (Dex)‑stimulated hBMSCs remains unknown. In the present study, the expression of LINC00473 was determined in the hBMSCs of patients with SONFH and control patients. In addition, the protective effects and underlying molecular mechanisms of LINC00473 in Dex‑stimulated hBMSCs were investigated. The results revealed that LINC00473 expression was significantly downregulated in hBMSCs from patients with SONFH compared with the controls, and that the upregulation of LINC00473 attenuated the inhibitory effects exerted by 1 µM Dex on the proliferation and apoptosis of hBMSCs. Moreover, the upregulation of LINC00473 significantly promoted the protein expression of phosphorylated (p‑)Akt, p‑Bcl‑2‑associated death promoter (p‑Bad) and B‑cell lymphoma 2 (Bcl‑2), whereas it decreased the cleavage of caspase‑3, thus preventing the Dex‑induced apoptosis of hBMSCs. Of note, the regulatory effects of LINC00473 on the Akt/Bad/Bcl‑2 signaling pathway and its anti‑apoptotic effects were similar to those of SC79 (an Akt activator), and were inhibited by MK‑2206 (an Akt inhibitor). In further experiments, it was found that the upregulation of LINC00473 markedly promoted the phosphorylation of Akt in Dex‑stimulated hBMSCs, and increased the protein level of phosphatidylethanolamine‑binding protein 1 (PEBP1). Alternatively, the promoting effect on Akt phosphorylation induced by LINC00473 was significantly attenuated following the knockdown of PEBP1. Furthermore, the upregulation of PEBP1 triggered a marked increase in the levels of Akt phosphorylation in Dex‑stimulated hBMSCs, which was line with the upregulation of LINC00473. Taken together, the results of the present study demonstrate that LINC00473 has the ability to rescue hBMSCs from Dex‑induced apoptosis through the PEBP1‑mediated activation of the Akt/Bad/Bcl‑2 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Jiang Y, Wang Y, Zhao Z and Li T: LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway. Int J Mol Med 47: 171-182, 2021.
APA
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., & Li, T. (2021). LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway. International Journal of Molecular Medicine, 47, 171-182. https://doi.org/10.3892/ijmm.2020.4788
MLA
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., Li, T."LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway". International Journal of Molecular Medicine 47.1 (2021): 171-182.
Chicago
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., Li, T."LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway". International Journal of Molecular Medicine 47, no. 1 (2021): 171-182. https://doi.org/10.3892/ijmm.2020.4788
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Jiang Y, Wang Y, Zhao Z and Li T: LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway. Int J Mol Med 47: 171-182, 2021.
APA
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., & Li, T. (2021). LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway. International Journal of Molecular Medicine, 47, 171-182. https://doi.org/10.3892/ijmm.2020.4788
MLA
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., Li, T."LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway". International Journal of Molecular Medicine 47.1 (2021): 171-182.
Chicago
Xu, Y., Jiang, Y., Wang, Y., Zhao, Z., Li, T."LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1‑mediated Akt/Bad/Bcl‑2 signaling pathway". International Journal of Molecular Medicine 47, no. 1 (2021): 171-182. https://doi.org/10.3892/ijmm.2020.4788
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