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

Cell proliferation

PubMedID: 22429763

Song ZC, Zhou W, Shu R, Ni J. Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1a pathway. Cell Prolif. 2012;45(3):239-48.
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 (CoCl(2)).

RESULTS
CoCl(2) induced cytotoxicity of human PDLCs in a concentration-dependent manner dependent on macromolecular synthesis, and resulted in apoptosis and mitochondrial dysfunction. CoCl(2) also induced redistribution of autophagy marker LC3, increased ratio of LC3-IIto LC3-Iand function of lysosomes. Furthermore, CoCl(2) promoted expression of HIF-1a following upregulation of expressions of Bnip3. Significant increases in expression of IL-1ß and MMP-8 were also observed. All these results were reversed by pre-treatment with antioxidant N-acetylcysteine.

CONCLUSIONS
Our data showed that CoCl(2) could induce cytotoxicity through mitochondria- apoptotic and autophagic pathways involved in HIF-1a. CoCl(2 -treated PDLCs may serve as an in vitro model for studies of molecular mechanisms in periodontitis.