Title: Intervertebral disc degeneration instigates vertebral endplate remodeling and facet joint pathology in a large animal model

Authors:  SE Gullbrand, BS Orozco, M Fainor, K Meadows, R Hilliard, M Boyes, S Mahindroo, RL Mauck, DM Elliott, TP Schaer, HE Smith

Address: Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, 19104 Philadelphia, PA, USA; Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, Perelman School of Medicine, University of Pennsylvania, 19104 Philadelphia, PA, USA

E-mail: sgullb at pennmedicine.upenn.edu; Harvey.Smith at uphs.upenn.edu

Abstract: Although the intervertebral discs are the most studied region of the spinal motion segment with respect to their degeneration and contributions to back pain, it is becoming increasingly evident that degeneration of adjacent structures including the facet joints, vertebral endplates and paraspinal muscles occurs concomitant with disc degeneration. However, crosstalk between these adjacent components of the motion segment remains understudied, particularly in preclinical large animal models. In this study, intervertebral disc degeneration was induced in goat cervical discs via intradiscal injection of 2U or 5U of chondroitinase ABC (ChABC). Disc degeneration and trans-endplate small molecule diffusion into the disc were assessed at 12 weeks using in vivo MRI T2 mapping and post-contrast enhanced T1 mapping. Animals were euthanized at 12 weeks post-ChABC injection for end-term structure-function analysis of the disc, vertebral endplate and facet tissues. Intradiscal injection of ChABC yielded a spectrum of disc degeneration independent of ChABC dosage. Increasing severity of disc degeneration correlated with increased vertebral endplate bone density. In levels that did not exhibit severe degeneration or endplate resorptions, we demonstrated a significant correlation between NP T2 values and disc diffusion properties. Early-stage osteoarthritis of the facet joints was observed concomitant with disc degeneration, characterized primarily by alterations in facet cartilage mechanical properties. This work established a large animal model of whole spinal motion segment degeneration, including correlations between trans-endplate diffusion and disc health, which can be utilized to increase the translational relevance of studies evaluating strategies for disc regeneration or repair.

Keywords: Goat model, crosstalk, osteoarthritis, disc nutrition.

Publication date: April 23th 2024

Article download: Pages 109-124 (PDF file)
DOI: 10.22203/eCM.v047a09