PMID- 29746847
OWN - NLM
STAT- MEDLINE
DCOM- 20180619
LR  - 20181202
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 205
DP  - 2018 Jul 15
TI  - CsA attenuates compression-induced nucleus pulposus mesenchymal stem cells 
      apoptosis via alleviating mitochondrial dysfunction and oxidative stress.
PG  - 26-37
LID - S0024-3205(18)30254-6 [pii]
LID - 10.1016/j.lfs.2018.05.014 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Li, Zhiliang
AU  - Li Z
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Chen, Songfeng
AU  - Chen S
AD  - Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou City 450052, China.
FAU - Ma, Kaige
AU  - Ma K
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Lv, Xiao
AU  - Lv X
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Lin, Hui
AU  - Lin H
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Hu, Binwu
AU  - Hu B
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - He, Ruijun
AU  - He R
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Shao, Zengwu
AU  - Shao Z
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China. Electronic address: 
      szwpro@163.com.
LA  - eng
PT  - Journal Article
DEP - 20180508
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Survival/drug effects
MH  - Cyclosporine/*pharmacology
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Intervertebral Disc Degeneration/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mesenchymal Stem Cells/*drug effects/ultrastructure
MH  - Mitochondrial Diseases/*drug therapy
MH  - Nucleus Pulposus/*cytology/drug effects
MH  - Oxidative Stress/*drug effects
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Cyclosporine A
OT  - Intervertebral disc degeneration (IVDD)
OT  - Mitochondrial dysfunction
OT  - Nucleus pulposus mesenchymal stem cells
OT  - Oxidative stress
EDAT- 2018/05/11 06:00
MHDA- 2018/06/21 06:00
CRDT- 2018/05/11 06:00
PHST- 2018/01/15 00:00 [received]
PHST- 2018/05/05 00:00 [accepted]
PHST- 2018/05/11 06:00 [pubmed]
PHST- 2018/06/21 06:00 [medline]
PHST- 2018/05/11 06:00 [entrez]
AID - S0024-3205(18)30254-6 [pii]
AID - 10.1016/j.lfs.2018.05.014 [doi]
PST - ppublish
SO  - Life Sci. 2018 Jul 15;205:26-37. doi: 10.1016/j.lfs.2018.05.014. Epub 2018 May 8.