Wednesday, May 8, 2024
5/8/2024
Project Summary The lumbar intervertebral discs naturally degenerate with age and are implicated in low back pain, the world’s leading cause of disability. Because the discs are avascular, cells residing in the central disc are up to 6-8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on diffusion and convection between the discs and adjacent vertebrae for nutrient transport and waste removal. When transport is compromised, local glucose and oxygen concentrations decrease, pH decreases, and cell viability and matrix turnover are impacted. Currently, there are no clinical strategies to intervene in age-related degeneration, but improving fluid transport may be one strategy to slow or reverse the process. Previous work in animals instrumented with external loading devices suggests that dynamic loading increases the rate of solutes transported into the discs and causes disc anabolism. One way to induce loading in vivo is through exercise and running exercise was recently related to improved disc health in animals and humans. Still, it is not clear how in vivo loading modulates fluid and nutrient transport and which exercise protocols induce the appropriate dynamic loads. Exercise dosing is likely an important factor, however there is a “complete lack of studies in the exercise and pain literature testing multiple doses of exercise in a single patient (or control) group”. The objective of this work is to identify factors that affect fluid and nutrient transport and implement an exercise protocol that optimizes transport for disc regeneration. In Aim 1, rats of young, adult, and advanced ages will be evaluated for differences in exercise-induced disc fluid transport and factors related to fluid transport (cartilage endplate porosity, disc deformations during activity) as well as exercise-induced cellular glucose uptake and factors that affect glucose uptake (cell membrane transporters). In Aim 2, rats of young and advanced ages will be evaluated while executing one of 6 8-week treadmill programs of varying intensity for changes in disc function, composition, structure, and pain. In Aim 3, rats with surgically-induced degeneration will be evaluated while executing an 8-week treadmill program for changes in disc function, composition, structure, and pain. There will be two control groups to determine the specific impact of exercise-induced loading. My goal is to develop a translational pipeline to test and iterate disc regeneration strategies in animals and seamlessly import those into humans. The results from this study will identify exercise protocols that maximize disc fluid transport, glucose uptake, and disc health and can be translated to humans for disc regeneration.
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