Degeneration alters structure‐function relationships at multiple length‐scales and across interfaces in human intervertebral discs

Abstract

Intervertebral disc (IVD) degeneration and associated back pain place a significant burden on the population. IVD degeneration is a progressive cascade of cellular, compositional, and structural changes, which results in a loss of disc height, disorganization of extracellular matrix architecture, tears in the annulus fibrosus which may involve herniation of the nucleus pulposus, and remodeling of the bony and cartilaginous endplates (CEP). These changes to the IVD often occur concomitantly, across the entire motion segment from the disc subcomponents to the CEP and vertebral bone, making it difficult to determine the causal initiating factor of degeneration. Furthermore, assessments of the subcomponents of the IVD have been largely qualitative, with most studies focusing on a single attribute, rather than multiple adjacent IVD substructures. The objective of this study was to perform a multiscale and multimodal analysis of human lumbar motion segments across various length scales and degrees of degeneration. We performed multiple assays on every sample and identified several correlations between structural and functional measurements of disc subcomponents. Our results demonstrate that with increasing Pfirrmann grade there is a reduction in disc height and nucleus pulposus T2 relaxation time, in addition to alterations in motion segment macromechanical function, disc matrix composition and cellular morphology. At the cartilage endplate‐vertebral bone interface, substantial remodeling was observed coinciding with alterations in micromechanical properties. Finally, we report significant relationships between vertebral bone and nucleus pulposus metrics, as well as between micromechanical properties of the endplate and whole motion segment biomechanical parameters, indicating the importance of studying IVD degeneration as a whole organ.

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration

“…Isolated motion segments were then subject to a compressive mechanical testing protocol consisting of 20 cycles of compression (0 to −750 N) at 0.05 Hz in a bath of phosphate buffered saline (PBS) with protease inhibitors. Mechanical properties (toe and linear region moduli and transition and maximal strains) normalized to disc area and height obtained from the MR images were calculated from the 20th cycle of compression, as previously described 20,22 …”

“…The compressive mechanical properties, NP T2 relaxation times, and disc height of the anterior portion of the motion segments were analyzed as described in our prior work, which characterized changes in these parameters over a spectrum of degeneration. 20 Briefly, after thawing, each donor spine underwent magnetic resonance imaging (MRI) scanning at 3T to acquire mid-sagittal T2weighted images to measure disc height and for Pfirrmann grading, 21 as well as a sequence of images for quantitative T2 mapping. Isolated motion segments were then subject to a compressive mechanical testing protocol consisting of 20 cycles of compression (0 to −750 N) at 0.05 Hz in a bath of phosphate buffered saline (PBS) with protease inhibitors.…”

Endplate role in the degenerative disc disease: A brief review

“…This arrangement is important for minimising the concentration of mechanical stress during complex loading, which comprises pressure, compressive forces and shear forces. As the cartilaginous portion of the endplate is not secured into the bony portion, this border may be detached or divided easily[ 65 - 68 ].…”

Regeneration in Spinal Disease: Therapeutic Role of Hypoxia-Inducible Factor-1 Alpha in Regeneration of Degenerative Intervertebral Disc

“…IVD degeneration is a progressive cascade of cellular, compositional, and structural changes [ 38 , 51 ]. Since IVD is an avascular tissue, glycolysis is the sole supply of cellular energy, which uses glucose and generates lactic acid [ 52 ].…”