The Role Of HSP70 In Oxidative Stress-Induced Apoptosis And Senescence Of Human Nucleus Pulposus Derived Stem Cells

Objective:The aims of the study was to investigate the protective effects of heat shock protein 70(HSP70)on oxidative stress-induced cellular damages of human nucleus pulposus stem cells(NPSCs),as well as possible underlying mechanisms.Methods:After extraction of NPSCs,the cells were divided into three groups:blank control group,tert-butyl hydroperoxide(t-BHP)group and t-BHP+HSP70 activation group.In HSP70 activation group,NPSCs were pre-treated with 1μM TRC051384 for 6 h.Then,both HSP70 activation group and control group were treated with t-BHP for 12 h.Cell viability,cell death,apoptosis,cellular reactive oxygen species(ROS)and mitochondrial ROS,mitochondrial membrane potential(MMP)and cell senescence was determined.In addition,we analyzed the expression of HSP70,mitochondrial apoptosis pathway,senescence-related proteins and the JNK/c-Jun pathway related proteins and HSPA1A,IL1B,IL6 and CXCL8(IL8)mRNA expression levels.Results:t-BHP dose-dependently and time-dependently impaired cell viability,caused oxidative stress,decreased MMP and induced apoptosis and senescence in NPSCs.Moreover,t-BHP resulted in an increase of HSP70 expression.However,HSP70 activation significantly alleviate those cellular damages induced by t-BHP via inhibiting the JNK/c-Jun pathway.Conclusion:Activation of HSP70 protect NPSCs from t-BHP-induced multiple types of cellular damages,which may provide a promising therapeutic target for intervertebral disc degeneration.