Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to muscle repair but whether platelets promote regeneration beyond their role in hemostasis remains unexplored. Here, we find that sign...

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Published inNature communications Vol. 14; no. 1; p. 2900
Main Authors Graca, Flavia A, Stephan, Anna, Minden-Birkenmaier, Benjamin A, Shirinifard, Abbas, Wang, Yong-Dong, Demontis, Fabio, Labelle, Myriam
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 22.05.2023
Nature Publishing Group UK
Nature Portfolio
Subjects
Angiogenesis
Animals
Chemokines
Chemotactic factors
Depletion
Hemostasis
Hemostatics
Infiltration
Inflammation
Injuries
Leukocytes (neutrophilic)
Male
Mice
Muscle strength
Muscle, Skeletal - physiology
Muscles
Musculoskeletal system
Neutrophil Infiltration
Neutrophils
Neutrophils - physiology
Platelets
Recruitment
Regeneration
Signaling
Skeletal muscle
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Summary:Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to muscle repair but whether platelets promote regeneration beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines is an early event necessary for muscle repair in mice. Platelet depletion reduces the levels of the platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase neutrophil infiltration to injured muscles is impaired whereas later inflammation is exacerbated. Consistent with this model, neutrophil infiltration to injured muscles is compromised in male mice with Cxcl7-knockout platelets. Moreover, neo-angiogenesis and the re-establishment of myofiber size and muscle strength occurs optimally in control mice post-injury but not in Cxcl7ko mice and in neutrophil-depleted mice. Altogether, these findings indicate that platelet-secreted CXCL7 promotes regeneration by recruiting neutrophils to injured muscles, and that this signaling axis could be utilized therapeutically to boost muscle regeneration.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-38624-0