Effect of vertebral endplate composition on disc health

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DESCRIPTION (provided by applicant): Although the exact origin of most cases of low back pain remains unknown, it is understood that degenerative damage to the intervertebral disc (IVD) plays a central role in the pathogenic mechanism leading to back pain. As the IVD is the largest avascular structure in the body, survival of disc cells is critically dependent on nutrient supply from capillaries within adjacent vertebra. A principal determinant of nutrient supply from capillary beds to disc cells is the vertebral endplate, which is composed of a hyaline cartilage layer and a subchondral bone layer that supports an extensive network of marrow contact channels (MCCs) through which capillary buds emerge. It is hypothesized that degenerative hypermineralization of the vertebral endplate is a central factor in restricting nutrient supply to the IVD, leading to disc degeneration. Nevertheless, whether this process is the result of subchondral bone hypermineralization and MCC occlusion, or instead due to calcification of the cartilage layer itself, remains unresolved. Identifying the component of the endplate that is most susceptible to hypermineralization is central to understanding the mechanism by which nutrient supply to the IVD is lost. We propose to determine the relationship between subchondral bone architecture, cartilaginous endplate composition and organization, and the initiation and progression of IVD degeneration in cadaveric human lumbar spines.