title: Pingyangmycin-induced in vivo lumbar disc degeneration model of rhesus monkeys.
abstract: METHODS
  Animal experimental study.
  
  
  OBJECTIVE
  To establish a slowly progressive and reproducible intervertebral disc degeneration model and determine the performance of T1ρ magnetic resonance imaging in the evaluation of disc degeneration.
  
  
  BACKGROUND
  Recently, one of the hotspots of research efforts was related to management of early stage of disc degeneration. To our knowledge, a functional animal model that mimics ischemic and slowly progressive disc degeneration of humans does not exist.
  
  
  METHODS
  The subchondral bone adjacent to the lumbar intervertebral discs (from L3-L4 to L6-L7) of 8 rhesus monkeys was randomly injected with 4 mL of Pingyangmycin (PYM) solution (1.5 mg/mL, PYM), or 4 mL of phosphate buffered saline (Vehicle control), or exteriorized but not injected anything (Sham), respectively. The degenerative process was investigated by using radiography and T1ρ magnetic resonance imaging at 1, 3, 6, 9, 12, and 15 months postoperatively. Histological scoring, immunohistochemistry, and real-time polymerase chain reaction were performed at 15 months.
  
  
  RESULTS
  The mean T1ρ values of nucleus pulposus and annulus fibrosus in the PYM group significantly decreased after 3 and 6 months, respectively, followed by slow decrease, and the histological score was significantly higher at 15 months, compared with the control groups. The results of molecular analysis revealed a significant increase matrix metalloprotease-3, A disintegrin and metalloproteinase with thrombospondin motifs -5, tumor necrosis factor α, interleukin-1β, interleukin-6 expressions, and marked reduction in aggrecan, type II collagen, von Willebrand factor expressions at the messenger RNA levels in the PYM group. Spearman correlation analysis of Pfirrmann grades showed significantly inverse correlation with T1ρ values of nucleus pulposus and annulus fibrosus (r = -0.634, -0.617, respectively, P < 0.01).
  
  
  CONCLUSIONS
  Injection of PYM into the subchondral bone adjacent to the lumbar intervertebral discs of rhesus monkeys can results in mild, slowly progressive disc degeneration, which mimics the onset of human disc degeneration, and the T1ρ magnetic resonance imaging is suited for evaluating intervertebral disc degeneration.
  
  
  METHODS
  N/A.
authors: *Department of Spine Surgery, the First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, Guangzhou, China †Orthopaedic Surgery, UT Southwestern Medical Center, Dallas, TX ‡The Medical School of Shenzhen University, Shenzhen, China; Departments of §Radiology and ¶Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China ‖Department of Biology, UT Southwestern Medical Center, Dallas, TX **Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and ††Department of Health Sciences, Cleveland Clinic, Cleveland, OH.
authors: Fuxin
authors: F
authors: Wei
authors: Rui
authors: R
authors: Zhong
authors: Le
authors: L
authors: Wang
authors: Zhiyu
authors: Z
authors: Zhou
authors: Ximin
authors: X
authors: Pan
authors: Shangbin
authors: S
authors: Cui
authors: Haixing
authors: H
authors: Sun
authors: Xuenong
authors: X
authors: Zou
authors: Manman
authors: M
authors: Gao
authors: Bo
authors: B
authors: Jiang
authors: Wenfang
authors: W
authors: Chen
authors: Wenquang
authors: W
authors: Zhuang
authors: Han
authors: H
authors: Sun
authors: Shaoyu
authors: S
authors: Liu
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D005260:Female; D055959:Intervertebral Disc Degeneration / Q000139:chemically induced* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male
chemical_list: D001761:Bleomycin; C025703:bleomycetin