Inflammatory cytokine and catabolic enzyme expression in a goat model of intervertebral disc degeneration

• Published in: Journal of orthopaedic research 2020-11, Vol.38 (11), p.2521-2531
• Main Authors: Zhang, Chenghao, Gullbrand, Sarah E., Schaer, Thomas P., Lau, Yian Khai, Jiang, Zhirui, Dodge, George R., Elliott, Dawn M., Mauck, Robert L., Malhotra, Neil R., Smith, Lachlan J.
• Format: Article
• Language: English
• Subjects: Animals; caprine; Cytokines - metabolism; Disease Models, Animal; Goats; inflammation; intervertebral disc degeneration; Intervertebral Disc Degeneration - diagnostic imaging; Intervertebral Disc Degeneration - enzymology; large animal model; Lumbar Vertebrae - diagnostic imaging; Lumbar Vertebrae - enzymology; Magnetic Resonance Imaging; Male; Metalloendopeptidases - metabolism; preclinical
• ISSN: 0736-0266; 1554-527X; 1554-527X
• DOI: 10.1002/jor.24639

Intervertebral disc degeneration is implicated as a leading cause of low back pain. Persistent, local inflammation within the disc nucleus pulposus (NP) and annulus fibrosus (AF) is an important mediator of disc degeneration and negatively impacts the performance of therapeutic stem cells. There is a lack of validated large animal models of disc degeneration that recapitulate clinically relevant local inflammation. We recently described a goat model of disc degeneration in which increasing doses of chondroitinase ABC (ChABC) were used to reproducibly induce a spectrum of degenerative changes. The objective of this study was to extend the clinical relevance of this model by establishing whether these degenerative changes are associated with the local expression of inflammatory cytokines and catabolic enzymes. Degeneration was induced in goat lumbar discs using ChABC at different doses. After 12 weeks, degeneration severity was determined histologically and using quantitative magnetic resonance imaging (MRI). Expression levels of inflammatory cytokines (tumor necrosis factor‐α [TNF‐α], interleukin‐1β [IL‐1β], and IL‐6) and catabolic enzymes (matrix metalloproteinases‐1 [MMPs‐1] and 13, and a disintegrin and metalloproteinase with thrombospondin type‐1 motifs‐4 [ADAMTS‐4]) were assessed as the percentage of immunopositive cells in the NP and AF. With the exception of MMP‐1, cytokine, and enzyme expression levels were significantly elevated in ChABC‐treated discs in the NP and AF. Expression levels of TNF‐α, IL1‐β, and ADAMTS‐4 were positively correlated with histological grade, while all cytokines and ADAMTS‐4 were negatively correlated with MRI T2 and T1ρ scores. These results demonstrate that degenerate goat discs exhibit elevated expression of clinically relevant inflammatory mediators, and further validate this animal model as a platform for evaluating new therapeutic approaches for disc degeneration.