title: Inflammatory cytokines induce caveolin-1/β-catenin signalling in rat nucleus pulposus cell apoptosis through the p38 MAPK pathway.
abstract: OBJECTIVE
  Apoptosis of nucleus pulposus (NP) cells is a major cause of intervertebral disc degeneration. To elucidate relationships between caveolin-1 and cytokine-induced apoptosis, we investigated the role of caveolin-1 in cytokine-induced apoptosis in rat NP cells and the related signalling pathway.
  
  
  METHODS
  Rat NP cells were treated with interleukin (IL)-1β or tumour necrosis factor alpha (TNF-α), and knockdown of caveolin-1 and β-catenin was achieved using specific siRNAs. Then, apoptotic level of rat NP cells and expression and activation of caveolin-1/β-catenin signalling were assessed by flow cytometric analysis, qRT-PCR, western blotting and luciferase assays. The relationship between the mitogen-activated protein kinase (MAPK) pathway and caveolin-1 promoter activity was also determined by luciferase assays.
  
  
  RESULTS
  IL-1β and TNF-α induced apoptosis, upregulated caveolin-1 expression and activated Wnt/β-catenin signalling in rat NP cells, while the induction effect of cytokines was reversed by caveolin-1 siRNA and β-catenin siRNA. Promotion of rat NP cell apoptosis and nuclear translocation of β-catenin induced by caveolin-1 overexpression were abolished by β-catenin siRNA. Furthermore, pretreatment with a p38 MAPK inhibitor or dominant negative-p38, blocked cytokine-dependent induction of caveolin-1/β-catenin expression and activity.
  
  
  CONCLUSIONS
  The results revealed the role of p38/caveolin-1/β-catenin in inflammatory cytokine-induced apoptosis in rat NP cells. Thus, controlling p38/caveolin-1/β-catenin activity seemed to regulate IL-1β- and TNF-α-induced apoptosis in the NP during intervertebral disc degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Jianxi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Fazhi
authors.initials: F
authors.lastname: Zang
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D051242:Caveolin 1 / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D020935:MAP Kinase Signaling System; D000070614:Nucleus Pulposus / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000276:immunology*
chemical_list: D051242:Caveolin 1; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin