Transport and Metabolism of Glucose in Intervertebral Disc

of a dissertation at the University of Miami. Dissertation supervised by Professor Weiyong Gu No. of pages in text. (164) Low back pain is a major social and economic dilemma in the United States. Despite its high impact, the origins of low back remain unclear. Nonetheless, degenerative changes to the intervertebral discs (IVD) of the spine have been implicated as a possible source leading to pain. Poor nutritional supply to the IVD is believed to play a primary role in the pathophysiology of disc degeneration. Since the disc is avascular, vital nutrients, such as glucose, must be supplied by surrounding blood vessels. However, the transport and metabolic properties of glucose in the IVD have not been fully delineated. This knowledge is necessary in order to elucidate the nutrition-related mechanisms of disc degeneration. Therefore, in this dissertation, experimental and theoretical methods are used to investigate the transport and metabolism of glucose in the intervertebral disc. Strain-dependent and anisotropic (i.e., direction-dependent) transport of glucose in human annulus fibrosus (AF) was investigated using custom apparatuses. Results indicate that diffusivity and partitioning of glucose in human AF decreases with increasing compressive strain. Furthermore, diffusivity of glucose is anisotropic, being lower in the radial direction than the axial or circumferential directions at all strain levels. Transport of glucose in human AF was also found to diminish with increasing disc degeneration. A new method was developed to measure the rate of glucose consumption by IVD cells; this method was then validated with porcine AF and nucleus pulposus (NP) cells at varying levels of oxygen tension. Results show a positive Pasteur effect, with the glucose consumption rate by AF and NP cells increasing at low levels of oxygen. Moreover, results indicate that the rate of consumption of glucose by NP cells is significantly higher than that by AF cells. A new, three-dimensional finite element model of the IVD was developed in order to theoretically predict nutrient distributions in the disc. This model incorporated anatomical disc geometry, nutrient transport coupled to cellular metabolism, and mechanical loading conditions. The model was used to investigate the effects of endplate calcification and in vivo loading conditions on glucose distributions in the disc. Both calcification and compressive loading resulted in diminished glucose concentrations in the tissue. The model was also used to analyze the effects of degeneration and compression on cell viability in IVD by incorporating viability criteria. Our model could predict cell death in degenerated tissue, and compressive loading augmented this effect. The model prediction can be used to supplement experimental results, and may also serve as a useful tool in developing new strategies for the treatment of disc degeneration. The findings of this dissertation greatly enhance the knowledge of glucose transport and metabolism in the intervertebral disc. Given that glucose is a critical nutrient for disc cell survival, this knowledge can provide important insight into nutritional pathways and mechanisms in the IVD, as well as related disc degeneration.