title: Upregulation of tumor necrosis factor α and ADAMTS-5, but not ADAMTS-4, in human intervertebral cartilage endplate with modic changes.
abstract: METHODS
  This study investigated the expression of 2 types of ADAMTS in human intervertebral cartilage endplate (CEP) and related mechanisms concerning tumor necrosis factor α (TNF-α)-induced nuclear factor κB signaling pathway.
  
  
  OBJECTIVE
  To determine which type of ADAMTS is more strongly expressed and the role of TNF-α in CEP.
  
  
  BACKGROUND
  ADAMTS-4 and ADAMTS-5 were proven to be essential in the degeneration of articular cartilage and intervertebral disc. CEP is an important structure adjacent to the disc. However, the activities of ADAMTS in CEP are unclear.
  
  
  METHODS
  CEPs were obtained from subjects after spinal surgery and categorized as members of either the Modic change group or the control group. Sections of these tissues were stained with hematoxylin-eosin, safranin O, and immunohistochemistry procedures for ADAMTS-4, ADAMTS-5, and TNF-α. Transcriptional levels of aggrecan, type I collagen, type II collagen, type X collagen, ADAMTS-4, ADAMTS-5, and TNF-α were investigated by quantitative real-time polymerase chain reaction. In addition, the effect of TNF-α on ADAMTS-5 and its potential mechanisms are investigated in cultured bovine endplate chondrocytes in vitro.
  
  
  RESULTS
  Our data demonstrated that the degenerative changes associated with the expression of extracellular matrix proteins were correlated with increased levels of ADAMTS-5, but not ADAMTS-4, in the CEP of patients with Modic changes. The expression levels of TNF-α in the Modic change group were significantly increased, which was correlated with the enhanced expression of ADAMTS-5. Additional in vitro investigation confirmed that TNF-α could upregulate the expression of ADAMTS-5 by activating nuclear factor κB pathway in cultured bovine endplate chondrocytes.
  
  
  CONCLUSIONS
  We conclude that the upregulation of TNF-α and ADAMTS-5, but not ADAMTS-4, may play an important role in degenerative CEP-induced low back pain.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China; and †Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Zhou
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Hu
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Wang
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Xu
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Fang
authors.forename: Shun-Wu
authors.initials: SW
authors.lastname: Fan
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D017116:Low Back Pain / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae; D008875:Middle Aged; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human