These authors contributed equally to the work.
Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1α pathway
Article first published online: 20 MAR 2012
© 2012 Blackwell Publishing Ltd
Volume 45, Issue 3, pages 239–248, June 2012
How to Cite
Song, Z.-C., Zhou, W., Shu, R. and Ni, J. (2012), Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1α pathway. Cell Proliferation, 45: 239–248. doi: 10.1111/j.1365-2184.2012.00810.x
- Issue published online: 17 APR 2012
- Article first published online: 20 MAR 2012
- Manuscript Accepted: 29 DEC 2011
- Manuscript Received: 21 NOV 2011
- National Nature Science Foundation of China. Grant Number: 30801292
- Shanghai Leading Academic Discipline Project. Grant Number: S30206
- Shanghai Municipal Science and Technology Commission. Grant Number: 11ZR1419300
- Shanghai Education Commission. Grant Number: 12YZ037
- National Defense Science and Technology Development Fund of Shanghai JiaoTong University. Grant Number: 11GFF50
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).
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.
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.