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Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1α pathway

Authors

  • Z.-C. Song,

    1. Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2. Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
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    • These authors contributed equally to the work.

  • W. Zhou,

    1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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    • These authors contributed equally to the work.

  • R. Shu,

    Corresponding author
    1. Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
    • Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • J. Ni

    1. Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2. Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
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Correspondence: R. Shu, Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; and Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China. Tel.: +86-21-23271699-5510; Fax: +86-21-63135412; E-mail: shurong123@hotmail.com

Abstract

Objectives

Oxygen deficiency caused by occlusal trauma and smoking can be present in patients with periodontitis. However, biochemical events important in periodontal tissues during hypoxia remain unclear. The aim of this study was to investigate effects of hypoxia on apoptosis and autophagy of human periodontal ligament cells (PDLCs) in vitro.

Materials and methods

Human PDLCs were obtained and cultured in vitro. Cell viability, apoptosis, autophagy and gene and protein expression were measured in presence and absence of cobalt chloride (CoCl2).

Results

CoCl2 induced cytotoxicity of human PDLCs in a concentration-dependent manner dependent on macromolecular synthesis, and resulted in apoptosis and mitochondrial dysfunction. CoCl2 also induced redistribution of autophagy marker LC3, increased ratio of LC3-IIto LC3-Iand function of lysosomes. Furthermore, CoCl2 promoted expression of HIF-1α following upregulation of expressions of Bnip3. Significant increases in expression of IL-1β and MMP-8 were also observed. All these results were reversed by pre-treatment with antioxidant N-acetylcysteine.

Conclusions

Our data showed that CoCl2 could induce cytotoxicity through mitochondria- apoptotic and autophagic pathways involved in HIF-1α. CoCl2-treated PDLCs may serve as an in vitro model for studies of molecular mechanisms in periodontitis.

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