Fig. 8. Platelets promote skeletal muscle regeneration by guiding the recruitment of neutrophils to injured muscles via the platelet-released chemokine CXCL7.

In response to injury, platelets localize to and form thrombi in skeletal muscles and promote the recruitment of neutrophils via the release of platelet-specific chemokines (e.g., CXCL7) that are neutrophil chemoattractants. Neutrophil infiltration is known to promote muscle repair via the removal of cellular debris and by setting the stage for the subsequent steps of regeneration, which include the infiltration of monocytes and macrophages and myogenesis, i.e., the de novo formation of myofibers. In the absence of platelets or when platelets lack CXCL7 (CXCL7KO), the recruitment of neutrophils to injured muscles is defective. This in turn leads to unresolved tissue damage, excessive recruitment of macrophages at later phases of regeneration, and to high levels of atrophic ligands that stunt the growth of newly-formed myofibers. Neo-angiogenesis is also reduced. Consequently, post-injury muscles arising from regeneration in the absence of early-stage platelet-initiated chemokine signaling display reduced myofiber size and lower muscle force production. Similar results are found with the experimental depletion of neutrophils. Altogether, these findings indicate a key role for platelet-induced chemokine signaling in ensuring optimal muscle regeneration by guiding the recruitment of neutrophils to injured muscles in the early phase after injury.