The Effect And Mechanism Of Autophagy In Compression-induced Senescence In Rat Annulus Fibrosus Cells

Background:Aging of annulus fibrosus(AF),which is a common feature of disc degeneration,may be caused by many cellular mechanisms.Our previous work indicated that compression could induce autophagy dysfunction and cellular damage in intervertebral disc cells.However,little is known about the relationship between autophagy and AF cell aging.Methods and Results:In the current study,we demonstrated that compression could induce premature senescence in AF cell,as reflected in increased senescence-associated-bgalactosidase(SA-b-gal)activity,senescence marker(p53 and p16)expression and G1 cycle arrest.The compression-induced senescence phenotype was prevented by pretreatment with starvation or rapamycin.Pretreatment with starvation or rapamycin prior to compression exposure also led to increased autophagic activity,as manifested in increased LC3 cleavage,Beclin-1 expression,and LC3-labeled autophagosome formation.Autophagy inhibition by 3-MA or CQ reduced the protective effects of starvation and rapamycin on compression-treated AF cells.Conclusion: Thus,the fndings of this study suggest that autophagy prevents comp ression stress-induced senescence in AF cells.