Exercise has been shown to influence nearly every tissue type in the body, including the hematopoietic system. The means by and the extent to which exercise is able to do this is unknown. Here, we investigated the effects of skeletal muscle and exercise on several components of hematopoiesis. Firstly, we investigated exercise induced changes in skeletal muscle endocrine signalling. We demonstrated that exercise increased skeletal muscle hypoxia, leading to HIF1α and HIF2α stability, resulting in increased expression of erythropoietin. As well, myoblasts in culture were shown to express and release erythropoietin in response to hypoxia. Secondly, we measured mobilization of hematopoietic cells during exercise. We demonstrated that exercise greatly increased the number of hematopoietic stem cells in circulation. The quantity of mobilization was dependent on exercise intensity, did not depend on fitness levels, and was at peak immediately post exercise. Thirdly, we measured levels of extramedullary hematopoiesis following exercise. Exercise increased spleen hematopoietic stem cell content. Furthermore, expression of genes associated with hematopoietic homing, adhesion, quiescence, and growth were all increased in the spleen following exercise. Finally, we examined bone marrow in the appendicular and axial skeleton of aged animals. Here, exercise increased bone marrow cellularity and reduced bone marrow adiposity in the appendicular skeleton of aged mice. However, lumbar vertebral marrow cellularity and skeletal muscle expression of hematopoietic cytokines in these mice was unaffected by exercise. Taken together, these results demonstrate that exercise is a potent mediator of hematopoietic homeostasis. Several themes recurrent in these and other studies lead to insight in how exercise is able to exert influence on hematopoiesis, namely: tissue specific changes in hematopoietic growth and homing factor expression, the ability of mechanical forces felt during exercise to alter the bone marrow niche microenvironment, and increased flux of hematopoietic stem cells through their various bodily niches. / Thesis / Doctor of Philosophy (PhD) / Exercise affects many different tissue types throughout the body. The hematopoietic system, through which the body produces blood cells, is no exception. How exercise as a stimulus is able to influence this system is poorly understood. Here, we demonstrate that exercise is able to stimulate skeletal muscle to produce erythropoietin, a potent hematopoietic growth factor. As well, we demonstrate that exercise is capable of mobilizing hematopoietic stem cells from the bone marrow to the blood. We then describe how exercise is able to increase hematopoietic activity outside the bone marrow. Finally, we show that exercise affects marrow in only certain bone marrow cavities. Our findings demonstrate that exercise is able to influence hematopoiesis in a myriad of ways. As well, our findings highlight potential commonalities in the means by which exercise exerts these influences.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21999 |
| Date | 11 1900 |
| Creators | Baker, Jeff |
| Contributors | Parise, Gianni, Kinesiology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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