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Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes

  • Authors:
    • Hongmei Meng
    • Tao Zhang
    • Weidong Liu
    • Huan Wang
    • Chunlei Wang
    • Zhe Zhao
    • Ning Liu
    • Wenbo Wang
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of Orthopedics, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China
    Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 351-358
    |
    Published online on: December 5, 2013
       https://doi.org/10.3892/ijmm.2013.1576
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Abstract

It has been reported that sodium fluoride (NaF) suppresses the proliferation and induces apoptosis of chondrocytes. However, the cellular and molecular mechanisms of the effect have not been elucidated. Therefore, the aim of this study was to evaluate the mechanisms of the effects of NaF on primary cultured rat chondrocytes in vitro. Chondrocytes were treated with NaF at concentrations of 0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mM. Cell viability decreased and the rate of apoptotic cells increased significantly with the gradient concentration of NaF in a time- and dose-dependent manner. Electron microscopy revealed cytoplasmic, organelle and nuclear alterations in the ultrastructure of chondrocytes exposed to various NaF concentrations. The cell cycle distribution was analyzed by flow cytometry, and the results indicated that NaF induced G2 cell cycle arrest. Western blotting was used to detect the apoptotic pathways. Downregulation of the Bcl-2 protein and upregulation of Bax, cleaved caspase-9, -12 and -3 proteins suggested that NaF was capable of inducing apoptosis through the mitochondrial and endoplasmic reticulum pathways. The results also showed that the levels of hypoxia-inducible factor 1α (HIF-1α), sex determining region Y box gene 9 (Sox9) and the collagen II (Col II) protein of the NaF groups were lower compared to those of the control groups. Thus, NaF may induce apoptosis through the downregulation of HIF-1α and disrupt the synthesis of extracellular matrix (ECM) through the downregulation of HIF-1α via the Sox9 pathway in primary cultured rat chondrocytes.
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Copy and paste a formatted citation
Spandidos Publications style
Meng H, Zhang T, Liu W, Wang H, Wang C, Zhao Z, Liu N and Wang W: Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes. Int J Mol Med 33: 351-358, 2014.
APA
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z. ... Wang, W. (2014). Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes. International Journal of Molecular Medicine, 33, 351-358. https://doi.org/10.3892/ijmm.2013.1576
MLA
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z., Liu, N., Wang, W."Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes". International Journal of Molecular Medicine 33.2 (2014): 351-358.
Chicago
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z., Liu, N., Wang, W."Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes". International Journal of Molecular Medicine 33, no. 2 (2014): 351-358. https://doi.org/10.3892/ijmm.2013.1576
Copy and paste a formatted citation
x
Spandidos Publications style
Meng H, Zhang T, Liu W, Wang H, Wang C, Zhao Z, Liu N and Wang W: Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes. Int J Mol Med 33: 351-358, 2014.
APA
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z. ... Wang, W. (2014). Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes. International Journal of Molecular Medicine, 33, 351-358. https://doi.org/10.3892/ijmm.2013.1576
MLA
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z., Liu, N., Wang, W."Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes". International Journal of Molecular Medicine 33.2 (2014): 351-358.
Chicago
Meng, H., Zhang, T., Liu, W., Wang, H., Wang, C., Zhao, Z., Liu, N., Wang, W."Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible factor-1α in primary cultured rat chondrocytes". International Journal of Molecular Medicine 33, no. 2 (2014): 351-358. https://doi.org/10.3892/ijmm.2013.1576
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