title: SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-α.
abstract: 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-α (TNF-α). 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-α. 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-α, 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-α alone. Our results therefore indicate that SP600125 improves the migration capacity of TNF-α-treated BMSCs and exerts a significant effect on the viability of TNF-α-treated BMSCs through reducing the up-regulation of p53, caspase-9/-3 and the Bcl-2 family induced by TNF-α. These findings suggest that SP600125 is of potential use in promoting the regeneration of bone and cartilage in OA and RA.
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Xizhuang
authors.initials: X
authors.lastname: Bai
authors.affiliation: 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.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology; D010003:Osteoarthritis / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Apoptosis; BMSCs; Migration; SP600125; TNF-α