Erythropoietin is a cytokine required for red blood cell formation. Erythropoietin receptor expression is not restricted to hematopoietic cells and erythropoietin activity extends beyond blood and includes neural protection and cardiac protection demonstrated in select animal models. We demonstrated erythropoietin receptor expression in skeletal muscle satellite cells but not in mature skeletal muscle fibers. Erythropoietin stimulates myoblast proliferation and modifies expression of MyoD and myogenin transcription factors to delay cell differentiation and fusion to myotubes. Erythropoietin response is lost with down regulation of its receptor after skeletal muscle differentiation. We hypothesized that erythropoietin administration or up regulation of its receptor on myoblasts can contribute to muscle maintenance and/or repair in skeletal muscle. Increasing erythropoietin receptor in myoblast cells increases cell survival particularly at reduced oxygen tension under serum starvation. Conversely, loss of erythropoietin receptor increases apoptosis under similar culture conditions. Increased erythropoietin receptor or erythropoietin signaling increased cell survival in myoblasts transplanted in vivo into the mdx mouse model for muscular dystrophy and restored dystrophin protein producing fibers. Therefore, increasing erythropoietin signaling promotes myblast survival in culture and myoblast function in a transplantation setting.
