title: A large animal model that recapitulates the spectrum of human intervertebral disc degeneration.
abstract: The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics.
  
  
  
  Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (μCT), and measurement of disc biomechanical properties.
  
  
  
  Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact.
  
  
  
  A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: S E
authors: SE
authors: Gullbrand
authors: Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: N R
authors: NR
authors: Malhotra
authors: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
authors: T P
authors: TP
authors: Schaer
authors: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
authors: Z
authors: Z
authors: Zawacki
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: J T
authors: JT
authors: Martin
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: J R
authors: JR
authors: Bendigo
authors: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: A H
authors: AH
authors: Milby
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: G R
authors: GR
authors: Dodge
authors: Penn State Hershey Bone and Joint Institute, Pennsylvania State University, Hershey, PA, United States.
authors: E J
authors: EJ
authors: Vresilovic
authors: Department of Biomedical Engineering, University of Delaware, Newark, DE, United States.
authors: D M
authors: DM
authors: Elliott
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.
authors: R L
authors: RL
authors: Mauck
authors: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, United States; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: lachlans@mail.med.upenn.edu.
authors: L J
authors: LJ
authors: Smith
mesh_terms: D000818:Animals; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D004195:Disease Models, Animal; D017587:Diskectomy, Percutaneous; D015511:Goat Diseases / Q000473:pathology; D006041:Goats; D006801:Humans; D007403:Intervertebral Disc / Q000187:drug effects / Q000601:surgery; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D011859:Radiography; D055114:X-Ray Microtomography
chemical_list: D019765:Chondroitin ABC Lyase
keywords: Caprine; Chondroitinase ABC; Disc degeneration; Goat; Nucleotomy; Preclinical animal model