title: IL-1β promotes ADAMTS enzyme-mediated aggrecan degradation through NF-κB in human intervertebral disc.
abstract: BACKGROUND
  The purpose of this study is to investigate IL-1β regulation of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS-5) expression through nuclear factor kappa B (NF-κB) in human nucleus pulposus (NP) cells.
  
  
  METHODS
  qRT-PCR and Western blot were used to measure ADAMTS expression. Transfections and gene silencing were used to determine the role of NF-κB on cytokine-mediated ADAMTS expression and its role in aggrecan degradation.
  
  
  RESULTS
  IL-1β increased ADAMTS expression in NP cells. Treatment with NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS expression. Silencing of p65 confirmed their role in IL-1β-dependent ADAMTS-4 and ADAMTS-5 expression and aggrecan degradation.
  
  
  CONCLUSIONS
  By controlling the activation of NF-κB signaling, IL-1β modulates the expression of ADAMTS in NP cells. To our knowledge, this is the first study that shows the contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells.
authors.affiliation: Department of Orthopedics, School of Medicine, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. sunzhy0008@163.com.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Spine and Joint Surgery, Central Hospital of Tai An, Shandong, China. hlb2038@163.com.
authors.forename: Zhanmin
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Orthopedics, School of Medicine, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. ortholiuchao@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, School of Medicine, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. lianghemxx@163.com.
authors.forename: He
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Orthopedics, School of Medicine, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. jiangminbo2007@163.com.
authors.forename: Minbo
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, School of Medicine, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. tjw609@163.com.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Tian
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000071096:ADAMTS Proteins; D000071121:ADAMTS4 Protein; D000328:Adult; D053674:Aggrecans / Q000378:metabolism*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D011348:Procollagen N-Endopeptidase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D053674:Aggrecans; D053583:Interleukin-1beta; D016328:NF-kappa B; D051996:Transcription Factor RelA; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C581035:ADAMTSL5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human