Open Access

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

  • Authors:
    • Wanlin Liu
    • Zhenqun Zhao
    • Yuyan Na
    • Chenyang Meng
    • Jianzhong Wang
    • Rui Bai
  • View Affiliations

  • Published online on: January 23, 2018     https://doi.org/10.3892/ijmm.2018.3412
  • Pages: 2028-2036
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Apoptosis of osteoblasts, triggered by prolonged or excessive use of glucocorticoids (GCs), has been identified as a dominant contributor to the development of osteoporosis and osteonecrosis. However, the molecular mechanisms underlying GC‑induced apoptosis are multifaceted and remain to be fully elucidated. The present study aimed to explore the correlation between dexamethasone (DEX)‑induced reactive oxygen species (ROS), autophagy and apoptosis in MC3T3‑E1 osteoblast‑like cells. Cell viability was assessed using a Cell Counting Kit‑8 assay, and flow cytometry was performed to assess cellular apoptosis, cell cycle and ROS production. Immunofluorescence and western blot analysis were respectively used to detect autophagic vacuoles and the expression of proteins, including cyclin D kinase (CDK)2, poly[ADP ribose] polymerase, caspase‑3, activating transcription factor (ATF)4, CCAAT/enhancer‑binding protein homologous protein (CHOP), Beclin1, microtubule‑associated proteins 1A/1B light chain (LC)3B and P62. It was revealed that DEX not only reduced cell viability, but also promoted apoptosis via the activation of endoplasmic reticulum (ER) stress. In addition, DEX induced cell cycle arrest at G0/G1 phase via inhibition of the expression of CDK2, and the production of ROS was activated. Of note, the DEX‑mediated changes in viability and apoptosis were attenuated in MC3T3‑E1 cells after treatment with 3‑methyladenine, which is an autophagy inhibitor. Treatment with the antioxidant N‑acetylcysteine abolished the effect of DEX on the proliferation, apoptosis, ER stress and autophagy of MC3T3‑E1 cells. In conclusion, the present results indicated that DEX promoted the production of ROS, which enhanced apoptosis through activation of autophagy and ER stress in MC3T3-E1 cells.
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April-2018
Volume 41 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Liu W, Zhao Z, Na Y, Meng C, Wang J and Bai R: Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells. Int J Mol Med 41: 2028-2036, 2018
APA
Liu, W., Zhao, Z., Na, Y., Meng, C., Wang, J., & Bai, R. (2018). Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells. International Journal of Molecular Medicine, 41, 2028-2036. https://doi.org/10.3892/ijmm.2018.3412
MLA
Liu, W., Zhao, Z., Na, Y., Meng, C., Wang, J., Bai, R."Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells". International Journal of Molecular Medicine 41.4 (2018): 2028-2036.
Chicago
Liu, W., Zhao, Z., Na, Y., Meng, C., Wang, J., Bai, R."Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells". International Journal of Molecular Medicine 41, no. 4 (2018): 2028-2036. https://doi.org/10.3892/ijmm.2018.3412