title: Resistin Promotes Intervertebral Disc Degeneration by Upregulation of ADAMTS-5 Through p38 MAPK Signaling Pathway.
abstract: METHODS
  Rat nucleus pulposus (NP) cells were activated with resistin with or without p38 mitogen-activated protein kinase (MAPK) pathway inhibition. The expression of a disintegrin and metalloprotease with thrombospondin motif-5 (ADAMTS-5), which plays an important role in intervertebral disc degeneration (IDD), was determined.
  
  
  OBJECTIVE
  The aim of this study was to demonstrate whether resistin can influence the ADAMTS-5 expression and to further investigate the underlying mechanisms.
  
  
  BACKGROUND
  Obesity has been demonstrated to promote IDD, whereas the exact mechanism remains poorly understood. Resistin, as an important adipokine, is increased with obesity and has been shown to play pro-inflammatory and catabolic role in cartilage metabolism. However, the effect of resistin on the catabolic enzymes within NP cells remains unknown.
  
  
  METHODS
  We exposed NP cells to resistin, and the transcriptional activity, gene expression, and protein levels of ADAMTS-5 were measured by luciferase reporter assay, qRT-polymerase chain reaction, immunofluorescence, and western blot, respectively. The activation of p38 MAPK pathways was detected using western blot analysis.
  
  
  RESULTS
  Resistin had no effect on cell viability. Resistin increased ADAMTS-5 expression in rat NP cells time and dose dependently. The p38 MAPK signaling pathway was activated after exposure to resistin. Treatment with p38 inhibitor decreased the upregulation of ADAMTS-5 by resistin.
  
  
  CONCLUSIONS
  The current study, for the first time, investigated the role of resistin in ADAMTS-5 regulation in IDD. These findings provide novel evidence supporting the causative role of obesity in IDD, which is important to develop novel preventative or therapeutic treatment in disc degenerative disorders.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Department of Orthopaedics, Affiliated Orthopaedics and Trauma Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Caijun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, Beijing Jishuitan Hospital, Peking University, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Orthopaedics, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, Beijing Jishuitan Hospital, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Anmin
authors.initials: A
authors.lastname: Jin
mesh_terms: D000071116:ADAMTS5 Protein / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D052243:Resistin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D052243:Resistin; D048051:p38 Mitogen-Activated Protein Kinases; D000071116:ADAMTS5 Protein; C093642:SB 203580