title: Survivin-TGFB3-TIMP1 Gene Therapy Via Lentivirus Vector Slows the Course of Intervertebral Disc Degeneration in an In Vivo Rabbit Model.
abstract: METHODS
  The ability of lentivirus vector (LV) survivin-transforming growth factor beta 3 (TGFB3)-tissue inhibitor of metalloproteinases 1 (TIMP1) on slowing disc degeneration was evaluated by an animal experiment.
  
  
  OBJECTIVE
  The aim of the study was to investigate the effect of LV survivin-TGFB3-TIMP1 on slowing disc degeneration in an in vivo rabbit model.
  
  
  BACKGROUND
  Cell apoptosis, increase of catabolic activity, and decrease of anabolic activity were the mechanisms of disc degeneration. Meanwhile, survivin, TGFB3, and TIMP1 can influence above process, respectively. However, there were no researches conducted to evaluate the effect of an LV containing all three proteins (referred to as LV-survivin-TGFB3-TIMP1) on slowing disc degeneration in vivo.
  
  
  METHODS
  Twenty skeletally mature female New Zealand White rabbits were randomly divided into four groups: nonpunctured sham surgical group (group A, n = 5), punctured blank control group (group B, n = 5), punctured empty vector control group (group C, n = 5), and the treatment group (group D, n = 5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, LV-carrying survivin, TGFB3, and TIMP1 were injected into the nucleus pulposus. Serial magnetic resonance imaging studies at 0, 3, and 12 weeks were performed. The rabbits were sacrificed at 12 weeks, and the histology, immunofluorescence, quantitative real-time polymerase chain reaction, Western blot, and caspase-3 activity was used for evaluation.
  
  
  RESULTS
  Magnetic resonance imaging, histology, gene expression, protein content, and apoptosis analyses of group A showed no disc degeneration. Groups B and C showed disc degeneration, which increased over time, and no significant difference was observed between the two groups (P > 0.05). In group D, there was less disc degeneration compared to the punctured control groups and the difference was statistically significant (P < 0.05).
  
  
  CONCLUSIONS
  The injection of LV-carrying survivin-TGFB3-TIMP1 into punctured rabbit intervertebral discs helps delay degenerative disc changes. Although data from animal models should be extrapolated to the human condition with caution, this study shows promise for gene therapy to decelerate disc degeneration.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yue
authors.forename: YaZhou
authors.initials: Y
authors.lastname: Lin
authors.forename: XueXiao
authors.initials: X
authors.lastname: Ma
authors.forename: HongFei
authors.initials: H
authors.lastname: Xiang
authors.forename: ChenSheng
authors.initials: C
authors.lastname: Qiu
authors.forename: JianHua
authors.initials: J
authors.lastname: Zhang
authors.forename: LongYang
authors.initials: L
authors.lastname: Li
authors.forename: BoHua
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D011817:Rabbits; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053782:Transforming Growth Factor beta3
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