A large animal model that recapitulates the spectrum of human intervertebral disc degeneration

• Published in: Osteoarthritis and cartilage 2017-01, Vol.25 (1), p.146-156
• Main Authors: Gullbrand, S.E, Malhotra, N.R, Schaer, T.P, Zawacki, Z, Martin, J.T, Bendigo, J.R, Milby, A.H, Dodge, G.R, Vresilovic, E.J, Elliott, D.M, Mauck, R.L, Smith, L.J
• Format: Article
• Language: English
• Subjects: Animals; Caprine; Chondroitin ABC Lyase - pharmacology; Chondroitinase ABC; Disc degeneration; Disease Models, Animal; Diskectomy, Percutaneous; Goat; Goat Diseases - pathology; Goats; Humans; Intervertebral Disc - drug effects; Intervertebral Disc - surgery; Intervertebral Disc Degeneration - diagnostic imaging; Intervertebral Disc Degeneration - pathology; Male; Nucleotomy; Preclinical animal model; Radiography; Rheumatology; X-Ray Microtomography
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2016.08.006

Summary Objective 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. Design 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. Results 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. Conclusions 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.