期刊
LIFE SCIENCES
卷 205, 期 -, 页码 26-37出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.05.014
关键词
Intervertebral disc degeneration (IVDD); Cyclosporine A; Nucleus pulposus mesenchymal stem cells; Mitochondrial dysfunction; Oxidative stress; Apoptosis
资金
- National Natural Science Foundation of China [81572203]
- National Key Research and Development Program of China [2016YFC1100100]
- Major Research Plan of National Natural Science Foundation of China [91649204]
Aims: This study aims to investigate the protective effects and potential mechanisms of cyclosporine A (CsA), which efficiently inhibits mitochondrial permeability transition pore (MPTP) opening, on compression-induced apoptosis of human nucleus pulposus mesenchymal stem cells (NP-MSCs). Materials and methods: Human NP-MSCs were subjected to various periods of 1.0 MPa compression. Cell viability was evaluated using cell counting kit-8 (CCK-8) assay. The cellular ultrastructure and ATP level were analyzed via transmission electron microscopy (TEM) and ATP detection kit respectively. The apoptosis ratio was determined using Annexin V/PI dual staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. The levels of apoptosis-associated molecules (cleaved caspase-3, Bax and Bcl-2) were analyzed by western blot and qRT-PCR. Additionally, MPTP opening, mitochondrial membrane potential (MMP) and the levels of oxidative stress-related indicators (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) were monitored. Key findings: Annexin V/PI dual staining and detection of apoptosis-associated molecules demonstrated that compression significantly up-regulated apoptosis level of NP-MSCs in a time-dependent manner. CsA greatly down-regulated compression-mediated NP-MSC apoptosis and the cell death ratio. Compression also notably exacerbated mitochondrial dysfunction, ATP depletion and oxidative stress in NP-MSCs, all of which were rescued by CsA. Significance: Our results demonstrated that CsA efficiently inhibited compression-induced NP-MSCs apoptosis by alleviating mitochondrial dysfunction and oxidative stress. These findings provide new insights into intervertebral disc (IVD) degeneration (IVDD), and suggest CsA treatment as a potential strategy for delaying or even preventing IVDD.
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