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Article

Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1

  • Authors:
    • Qing Chang
    • Mingliang Ji
    • Chao Li
    • Rui Geng
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China
  • Pages: 2123-2131
    |
    Published online on: June 30, 2020
       https://doi.org/10.3892/mmr.2020.11289
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Abstract

Osteoarthritis (OA) is one of the most common degenerative disease in elderly patients worldwide. Numerous microRNAs (miRs) have been reported to serve an important role in the regulation of gene expression in the occurrence and development of OA. The present study aimed to explore the effect of miR‑486‑5p on lipopolysaccharide (LPS)‑induced cell damage in chondrocytes, as well as the underlying mechanism. The ATDC5 cell line was treated with increasing concentrations of LPS (0, 1, 2, 4 and 8 µg/ml) for 6 h. The binding site of miR‑486‑5p on nuclear factor erythroid 2 like 1 (NRF1) was predicted using the miRDB database and was validated using the luciferase reporter assay. A CCK‑8 assay and flow cytometry analysis were conducted to determine cell viability and apoptosis, respectively. The level of inflammatory cytokines and oxidative stress‑associated factors were detected using corresponding test kits. Furthermore, the expression of associated genes were detected using reverse transcription‑quantitative PCR and western blotting. LPS significantly decreased cell proliferation, induced cell apoptosis and aggravated the inflammatory response and oxidative stress. Furthermore, miR‑486‑5p and NRF1 were significantly upregulated and downregulated, respectively, in LPS‑induced ATDC5 cells. miR‑486‑5p was identified to directly target and regulate the expression of NRF1. Inhibition of miR‑486‑5p significantly improved cell proliferation, decreased apoptosis, attenuated the production of inflammatory cytokines, regulated the level of reactive oxygen species, malondialdehyde, superoxide dismutase and lactate dehydrogenase, and improved the activity of antioxidant enzyme. Furthermore, the effect of miR‑486‑5p on LPS‑induced cell damage was diminished following the downregulation of NRF1. To conclude, inhibition of miR‑486‑5p alleviated LPS‑induced cell damage, including inflammatory injury, oxidative stress and apoptosis, in ATDC5 cells by targeting NRF1. Therefore, NRF1 may serve as a novel therapeutic target for OA.
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Copy and paste a formatted citation
Spandidos Publications style
Chang Q, Ji M, Li C and Geng R: Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1. Mol Med Rep 22: 2123-2131, 2020.
APA
Chang, Q., Ji, M., Li, C., & Geng, R. (2020). Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1. Molecular Medicine Reports, 22, 2123-2131. https://doi.org/10.3892/mmr.2020.11289
MLA
Chang, Q., Ji, M., Li, C., Geng, R."Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1". Molecular Medicine Reports 22.3 (2020): 2123-2131.
Chicago
Chang, Q., Ji, M., Li, C., Geng, R."Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1". Molecular Medicine Reports 22, no. 3 (2020): 2123-2131. https://doi.org/10.3892/mmr.2020.11289
Copy and paste a formatted citation
x
Spandidos Publications style
Chang Q, Ji M, Li C and Geng R: Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1. Mol Med Rep 22: 2123-2131, 2020.
APA
Chang, Q., Ji, M., Li, C., & Geng, R. (2020). Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1. Molecular Medicine Reports, 22, 2123-2131. https://doi.org/10.3892/mmr.2020.11289
MLA
Chang, Q., Ji, M., Li, C., Geng, R."Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1". Molecular Medicine Reports 22.3 (2020): 2123-2131.
Chicago
Chang, Q., Ji, M., Li, C., Geng, R."Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1". Molecular Medicine Reports 22, no. 3 (2020): 2123-2131. https://doi.org/10.3892/mmr.2020.11289
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