Endplate permeability and spinal disc degeneration

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DESCRIPTION (provided by applicant): Intervertebral disc degeneration is a significant source of pain and disability among US adults. While the etiology is varied and unknown in many patients, there is growing evidence that poor disc nutrition is an important precipitating factor. This is because the disc is the largest avascular tissue in the human body, and disc cell nutrition is critically dependent on diffusion from nearby tissues. Among the disc sub-tissues, the nucleus pulposus is the farthest from its nutrient supply (approximately 5 mm from capillaries in adjacent vertebra), and its dysfunction is implicated as an early common event in the overall degeneration cascade. The vertebral endplate is a hyaline cartilage layer that separates the nucleus from vertebral capillaries, and current theories state that decreasing endplate permeability (due to hypermineralization) causes decreasing nucleus cellularity and degradation in nuclear physical properties. Yet, there are no quantitative data that define how endplate permeability changes with age, degeneration, or spinal level. There is growing interest in tissue engineering approaches for disc repair that include rebuilding the nucleus pulposus by augmenting disc cell numbers (via cell transplantation) and signaling these cells to secrete vital matrix components (via gene or growth factor therapy). However, for this tactic to be successful, nutrient transport must keep up with the demands of increased cell numbers and metabolism. Yet, by definition this cannot happen if poor nutrition initiated degeneration in the first place. The goal of this proposal is to harvest endplates from 180 human discs, measure their permeability, and relate this to specimen specific variables that include subchondral bone porosity and hyaline cartilage biochemistry and structure. Endplate permeability will also be related to nucleus cellularity and overall disc degeneration to test the hypothesis that poor disc nutrition via decreased endplate permeability is an important etiologic factor for disc degeneration. We will also define the nucleus cellularity and endplate permeability compatible with healthy disc architecture. These data will be important to clarify the role of compromised nutrition in disc degeneration, and to specify whether endplate permeability modification is necessary to augment successful tissue engineering approaches for disc repair.