MITOCHONDRIAL CONTRIBUTIONS TO BONE HEALTH, AN INVESTIGATION USING TWO DIFFERENT ANIMAL MODELS OF MITOCHONDRIAL CAPACITY

Abstract

<p>Mitochondrial dysfunction has been linked to a number of age-associated disorders and recent evidence has shown that mitochondrial function is necessary for osteoblast differentiation and osteoclast survival. Although bone tissue was once thought to be an ‘inert’ tissue, research from the past decade in bone metabolism has demonstrated pathways linking bone and whole body energy metabolism. However, with mitochondria being the central energy provider in cells there is a paucity of research exploring the impact of mitochondrial function on bone tissue, with the bulk of work focused in cell culture. This thesis aimed to explore mitochondrial content and function after endurance training and an exhaustive bout of running in two different animal models. The first study explored the effect of progressive mitochondrial dysfunction on mitochondrial gene expression and bone strength in the polymerase gamma mouse model of mitochondrial dysfunction. The therapeutic efficacy of endurance training on mitochondrial parameters and bone strength were evaluated as well. The second study utilized the Koch-Britton rat model of low capacity and high capacity runners. This model has demonstrated that selection for low and high running capacity has led to a significant divergence in mitochondrial content and function between these two groups. Mechanical strain in the form of exercise has been established as playing a key role in regulating bone health however the underlying mechanisms are still being described. The untrained status and inherent differences in aerobic capacity allow for the elucidations of bone adaptations that may be a result of aerobic capacity. The effect of an exhaustive bout of exercise on mitochondrial gene expression and enzyme activity in LCR and HCR rats was studied. Taken together these studies demonstrate that exercise is beneficial for promoting bone health and may do so by altering mitochondrial content and stress resistance through the FoxO family of transcription factors.</p>