title: Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration.
abstract: METHODS
  IL-1β (interleukin-1β) can activate human nucleus pulposus cells with or without nuclear factor kappa B (NF-κB) inhibition. We undertook a descriptive and mechanistic investigation of catabolic effects of NF-κB signaling pathway in intervertebral disc degenerative changes.
  
  
  OBJECTIVE
  To clarify the mediatory role of NF-κB signaling pathway in human intervertebral disc degeneration (IDD).
  
  
  BACKGROUND
  IDD is a major cause of lower back pain, but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors that play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic activation of NF-κB in many degenerative diseases, but its role in IDD has not been adequately explored.
  
  
  METHODS
  Human nucleus pulposus cells in monolayer culture were exposed to IL-1β, which increases matrix-degrading enzyme activity in the nucleus pulposus, with or without NF-κB inhibition by BAY11-7082; ribonucleic acid was isolated for real-time polymerase chain reaction analysis of gene expression, Western blot analysis was performed to detect the changes of protein expression.
  
  
  RESULTS
  NF-κB specific inhibitor BAY11-7082 significantly inhibited IL-1β-induced NF-κB activation. IL-1β-dependent gene upregulation of matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5 was significantly reduced by NF-κB inhibition. The decreased gene expression of aggrecan and type II collagen, induced by IL-1β was also reversed by BAY11-7082. NF-κB inhibition reversed the IL-1β-induced changes of protein expression of MMP-3, MMP-9, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and type II collagen.
  
  
  CONCLUSIONS
  These findings demonstrate that the NF-κB signaling pathway is a key mediator of IDD and represents a therapeutic target for mitigating disc degenerative diseases.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopedics, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, School of Medicine, Shanghai, China; and †Department of Paediatrics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Zhongyi
authors.forename: Zhao
authors.initials: Z
authors.lastname: Sai
authors.forename: Liu
authors.initials: L
authors.lastname: Chao
authors.forename: Tian
authors.initials: T
authors.lastname: Jiwei
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D053583:Interleukin-1beta; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones