eCM Journal - Manuscript - Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system -True Open Access

2020 Volume No 40 – pages 21-37

Title: Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system

Authors: CME Rustenburg, JW Snuggs, KS Emanuel, A Thorpe, C Sammon, CL Le Maitre, TH Smit

Address: Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield S1 1WB, UK

E-mail: C.Lemaitre at shu.ac.uk

Abstract: Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration.
Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression.
Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1β, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.

Key Words: Intervertebral disc, loaded disc culture system, goat, disease model, moderate disc degeneration.

Publication date: July 16th 2020

Article download: Pages 21-37 (PDF file)
DOI: 10.22203/eCM.v040a02

Notes on corrected Fig. 4

Fig. 4 correction: Images for the control discs had been mistakenly labelled during image capture on the original figure and incorrect images included within the original figure; this has been corrected on the revised.

Fig. 4: All analysis and conclusions were drawn from the original slides and not from individual images; thus, there are no changes required for the text of the article.