Sarah Daggs

Document Type

Honors Thesis


Bone and muscle crosstalk is a newly emerging field that focuses on the ability of bone cells and muscle cells to communicate with each other through mechanical and biochemical mechanisms. Until recently, the secretory function of both bone and muscle cells has largely been unexplored. My thesis focuses on continuing my faculty mentor’s current research on bone-muscle crosstalk by analyzing the effects of WNT3a, an important bone-secreted factor of the Wnt/β-catenin pathway, on myogenesis. Myogenesis is the process of producing muscle cells from stem cells in the embryonic stages of development and the regeneration of muscle tissue after cell injury or atrophy occurs (23). The primary goal was to determine the significance of WNT3a’s function in promoting primary myoblast differentiation, building on research from a previous cell line (C2C12). I found that at concentrations ranging from 10 ng/mL to 20 ng/mL of WNT3a, the myogenic differentiation was increased when compared to the controls. RT-qPCR experiments revealed that several gene expressions were affected, including the increased expression of the Muscle Regulatory Factors (MRF) MyoD and MyoG and the decreased expression of the most potent genetic inhibitor of muscle growth, myostatin. I discuss the broader implications of our findings in the context of the twin diseases of aging, sarcopenia and osteoporosis, as well as other musculoskeletal diseases such as muscular dystrophy. While our studies are still pilot in nature, molecules secreted by bone cells that can beneficially affect skeletal muscles might have a potential impact on the treatment of sarcopenia, osteoporosis and other musculoskeletal diseases. The basic studies we conducted are needed for the transition from translational, to bench research, to ultimately the bedside, since any treatment that can affect myogenesis could in turn affect how muscles recover from injury and atrophy. Our studies could pave the way for future pharmacological interventions and new diet and exercise modalities that might lead to the elevation of WNT3a in bones and muscles. Therefore, our studies are in agreement with the Strategic Plan of the National Institute of Nursing Research (NINR), Advancing Science: Improving Lives.

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