PMID- 27233606
OWN - NLM
STAT- MEDLINE
DCOM- 20170516
LR  - 20181202
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 475
IP  - 4
DP  - 2016 Jul 8
TI  - SP600125 enhances the anti-apoptotic capacity and migration of bone marrow 
      mesenchymal stem cells treated with tumor necrosis factor-alpha.
PG  - 301-7
LID - S0006-291X(16)30815-4 [pii]
LID - 10.1016/j.bbrc.2016.05.107 [doi]
AB  - Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic disorders 
      associated with inflammation of joints characterized by damage to the underlying 
      cartilage and bone. Bone marrow mesenchymal stem cells (BMSCs) are candidates for 
      regeneration of bone and cartilage, which is inhibited by inflammatory cytokines 
      in OA and RA, in particular tumor necrosis factor-alpha (TNF-alpha). This study aimed to 
      investigate if the c-Jun N-terminal kinases (JNK)-specific inhibitor SP600125 
      could enhance the anti-apoptosis and migration of BMSCs treated with TNF-alpha. The 
      level of apoptosis was evaluated via terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL)/4',6-diamidino-2-phenylindole 
      (DAPI) staining, annexin V/propidium iodide (PI) staining and western blotting. 
      Migration of BMSCs was assessed using transwell migration chambers. We showed 
      that the survival capacity and migration of BMSCs was significantly inhibited by 
      TNF-alpha, which was blocked by pretreatment with SP600125. In the presence of 
      SP600125, expression of cleaved caspase-9/-3 and p53 as well as the ratio of Bax 
      to Bcl-2 was significantly decreased compared to treatment with TNF-alpha alone. Our 
      results therefore indicate that SP600125 improves the migration capacity of 
      TNF-alpha-treated BMSCs and exerts a significant effect on the viability of 
      TNF-alpha-treated BMSCs through reducing the up-regulation of p53, caspase-9/-3 and 
      the Bcl-2 family induced by TNF-alpha. These findings suggest that SP600125 is of 
      potential use in promoting the regeneration of bone and cartilage in OA and RA.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Wei, Bo
AU  - Wei B
AD  - Department of Orthopedics, The People's Hospital of China Medical University, 
      Shenhe, Shenyang, Liaoning 110016, China; Department of Sports Medicine and Joint 
      Surgery, The People's Hospital of China Medical University, Shenhe, Shenyang, 
      Liaoning 110016, China.
FAU - Bai, Xizhuang
AU  - Bai X
AD  - Department of Orthopedics, The People's Hospital of China Medical University, 
      Shenhe, Shenyang, Liaoning 110016, China; Department of Sports Medicine and Joint 
      Surgery, The People's Hospital of China Medical University, Shenhe, Shenyang, 
      Liaoning 110016, China. Electronic address: bxzcmu2016@sina.com.
FAU - Chen, Kang
AU  - Chen K
AD  - Department of Orthopedics, The People's Hospital of China Medical University, 
      Shenhe, Shenyang, Liaoning 110016, China; Department of Sports Medicine and Joint 
      Surgery, The People's Hospital of China Medical University, Shenhe, Shenyang, 
      Liaoning 110016, China.
FAU - Zhang, Xiaonan
AU  - Zhang X
AD  - Department of Orthopedics, The People's Hospital of China Medical University, 
      Shenhe, Shenyang, Liaoning 110016, China; Department of Sports Medicine and Joint 
      Surgery, The People's Hospital of China Medical University, Shenhe, Shenyang, 
      Liaoning 110016, China.
LA  - eng
PT  - Journal Article
DEP - 20160524
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Anthracenes)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anthracenes/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Arthritis, Rheumatoid/drug therapy
MH  - Cell Movement/*drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors
MH  - Mesenchymal Stem Cells/*drug effects/immunology
MH  - Osteoarthritis/drug therapy
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*immunology
OTO - NOTNLM
OT  - Apoptosis
OT  - BMSCs
OT  - Migration
OT  - SP600125
OT  - TNF-alpha
EDAT- 2016/05/29 06:00
MHDA- 2017/05/17 06:00
CRDT- 2016/05/29 06:00
PHST- 2016/05/15 00:00 [received]
PHST- 2016/05/21 00:00 [accepted]
PHST- 2016/05/29 06:00 [entrez]
PHST- 2016/05/29 06:00 [pubmed]
PHST- 2017/05/17 06:00 [medline]
AID - S0006-291X(16)30815-4 [pii]
AID - 10.1016/j.bbrc.2016.05.107 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Jul 8;475(4):301-7. doi: 
      10.1016/j.bbrc.2016.05.107. Epub 2016 May 24.