Signaling roles of platelets in skeletal muscle regeneration

Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored in platelet & alpha;-granules and dense granules are released upon platelet activation and clotting. Emerging evidence indicates that such platelet-derived signaling factors are instrumental in guiding tissue regeneration. Here, we discuss the important roles of platelet-secreted signaling factors in skeletal muscle regeneration. Chemokines secreted by platelets in the early phase after injury are needed to recruit neutrophils to injured muscles, and impeding this early step of muscle regeneration exacerbates inflammation at later stages, compromises neo-angiogenesis and the growth of newly formed myofibers, and reduces post-injury muscle force production. Platelets also contribute to the recruitment of pro-regenerative stromal cells from the adipose tissue, and the platelet releasate may also regulate the metabolism and proliferation of muscle satellite cells, which sustain myogenesis. Therefore, harnessing the signaling functions of platelets and the platelet secretome may provide new avenues for promoting skeletal muscle regeneration in health and disease. Skeletal muscles have the remarkable capacity to regenerate in response to damage, and this requires the infiltration of neutrophils and, subsequently, of other immune cells to the injured muscle. How neutrophils are recruited to the site of muscle damage was, however, largely unknown. This minireview reports the emerging evidence that signaling factors secreted by platelets are key for the recruitment of neutrophils to injured muscles and for the subsequent regeneration and re-establishment of muscle homeostasis.image