PT  - JOURNAL ARTICLE
AU  - Ryan Borem
AU  - Joshua Walters
AU  - Allison Madeline
AU  - Lee Madeline
AU  - Jeremiah Easley
AU  - Sanjitpal Gill
AU  - Jeremy Mercuri
TI  - A pilot investigation of chemonucleolysis-induced intervertebral disc degeneration in the ovine lumbar spine
AID  - 10.1101/384743
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 384743
4099  - http://biorxiv.org/content/early/2018/08/03/384743.short
4100  - http://biorxiv.org/content/early/2018/08/03/384743.full
AB  - Intervertebral disc (IVD) degeneration (IVDD) initiates in the nucleus pulposus (NP) and is marked by elevated levels of pro-inflammatory cytokines and matrix-degrading proteases, leading to structural and functional disruption. IVDD therapeutics are currently being investigated; however, such approaches require validation using large animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Others have previously utilized intradiscal administration of chondroitinase-ABC (C-ABC) to initiate IVDD in the NP of sheep lumbar IVDs. While these studies examined changes in IVD height, hydration, and tissue micro-architecture, changes in biochemical content and mechanical properties were not assessed. Thus, the objective herein was to comprehensively characterize this ovine model IVDD for salient features reported in human degenerate IVDs by evaluating biochemical, biomechanical, and histological changes. Briefly, C-ABC (1U) was administered via intradiscal injection into the L1/2, L2/3, and L3/4 IVDs, and degeneration was assessed at 6- and 10-weeks via longitudinal magnetic resonance (MR) imaging. After 6 weeks, degenerative samples showed significant reductions in IVD heights (p=0.048) and MR imaging index (p=0.048), which worsened at 10 weeks. Post-mortem degenerate and controls IVDs were evaluated for differences in interleukin-1β concentration, axial and torsional functional spinal unit kinematics, and histological microarchitecture. Degenerate IVDs demonstrated significantly elevated concentrations of interleukin-1β (p=0.002). Additionally, degenerative samples showed increased creep displacement (p=0.022) and compressive stiffness’s (p=0.007) concurrent with decreased long-term elastic (p=0.007) and viscous dampening coefficients (p=0.002). Histological analysis of degenerative IVDs showed changes in microarchitecture, including derangement of the nucleus pulposus and annulus fibrosus tissue as well as cartilaginous end-plate irregularities. This pilot study demonstrated that intradiscal injection of 1U C-ABC induces significant and progressive degeneration of sheep lumbar IVDs over the time course investigated. The changes observed in this pilot’s study small sample size resemble the hallmarks of moderate to severe IVD degeneration observed in humans. Further study is warranted on a larger sample size to further validate these findings.