Intervertebral Disc Restoration Following Reduced Nucleus Pulposus Glycosaminoglycan in an Animal Model of Early Degeneration

3 Department of Orthopaedics, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY A lack of understanding of the degeneration process has limited treatments aimed at halting or reversing intervertebral disc degeneration. An animal model that replicates key features of human disc degeneration is needed for both elucidating the mechanisms as well as for preclinical testing of therapeutic strategies. The objective of the current work was to investigate the chronic outcomes in an in vivo model in the rat lumbar disc that simulates the diminished glycosaminoglycan and altered mechanics observed in early human disc degeneration. The model had previously been shown to closely resemble early stages of degeneration, yet whether or not the progression to a more severe state occurred was unknown. Rat lumbar intervertebral discs received an injection of a small dose of chondroitinase ABC and evaluated after 24 weeks using microCT to examine disc geometry and abnormal calcifications, disc mechanics, and nucleus glycosaminoglycan content. Additionally, the contribution of aggrecan catabolism was investigated at 4, 12, and 24 weeks through western blots for aggrecan neo-epitope species. Disc height, neutral zone modulus, and range of motion changes that were present at earlier time points were no longer present at 24 weeks. Nucleus glycososaminoglycan remained significantly decreased by 20% relative to controls; however, the magnitude of the decrease was reduced compared to earlier timepoints. The diminished detection of MMP cleaved aggrecan FFGVG fragments after ChABC injection indicates decreased catabolic activity may play a role in the observed restoration of disc properties and function. In summary, an in vivo animal model of early degeneration-like changes was shown to recover towards control levels by 24 weeks. Further work with this model may prove fruitful in defining potential targets for halting or reversing early human degeneration.