title: In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey.
abstract: BACKGROUND
  Recently, biological therapies for early intervention of degenerative disc disease have been introduced and developed; however, a functional animal model that mimics slowly progressive disc degeneration of humans does not exist. The objective of this study was to establish a slowly progressive and reproducible intervertebral disc (IVD) degeneration model.
  
  
  METHODS
  The subchondral bone adjacent to the lumbar IVDs (L3/4 and L5/6) of ten rhesus monkeys was randomly injected with 4 ml bleomycin solution (1.5 mg/ml), or 4 ml phosphate buffer saline (PBS) per segment as control, respectively. The degenerative process was investigated by using radiography and T1ρ MR imaging at 1, 3, 6, 9, 12 and 15 months postoperatively. Histological scoring, Sulfated Glycosaminoglycans (GAGs) analysis and real-time PCR were performed at 15 months. The correlation between histological score, GAGs and T1ρ values were also analyzed.
  
  
  RESULTS
  The results showed that the mean T1ρ values of nucleus pulposus (NP) and annulus fibrosus (AF) in the bleomycin group significantly decreased after 3 and 6 months respectively, followed by slowly decrease until at 15 months. At 15 months, the histological scores was significantly higher, and the GAGs of NP was significantly lower in the bleomycin group, compared with the control group (P<0.05). The results of real-time PCR revealed a significant increase in matrix metalloprotease (MMP)-3, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, tumor necrosis factor α, interleukin-1β, interleukin-6 expressions, transforming growth factor (TGF-β1) and marked reduction in aggrecan, type II collagen, von willebrand factor (vWF) expressions at the mRNA levels in the bleomycin group. Spearman correlation analysis showed a strong positive correlation between GAGs and T1ρ values of NP (r =0.740, P<0.01), and a significant inverse correlation between histological score and T1ρ values of NP and AF (r=-0.761, r=-0.729, respectively, P<0.01).
  
  
  CONCLUSIONS
  Injection of bleomycin into the subchondral bone adjacent to the lumbar IVDs of rhesus monkeys can results in mild, slowly progressive disc degeneration, which mimics the onset of human disc degeneration. T1ρ MR imaging is an effective and noninvasive technique for assessment of early stage disc degeneration.
authors.forename: Fuxin
authors.initials: F
authors.lastname: Wei
authors.forename: Rui
authors.initials: R
authors.lastname: Zhong
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhou
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Ximin
authors.initials: X
authors.lastname: Pan
authors.forename: Shangbin
authors.initials: S
authors.lastname: Cui
authors.forename: Xuenong
authors.initials: X
authors.lastname: Zou
authors.forename: Manman
authors.initials: M
authors.lastname: Gao
authors.forename: Haixing
authors.initials: H
authors.lastname: Sun
authors.forename: Wenfang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, the First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, Guangzhou, China. gzsyliu@tom.com.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001761:Bleomycin; D004195:Disease Models, Animal; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D011859:Radiography; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006025:Glycosaminoglycans; D001761:Bleomycin; C013786:A73025