title: The CXCR4/SDF1 axis improves muscle regeneration through MMP-10 activity.
abstract: The CXCR4/SDF1 axis participates in various cellular processes, including cell migration, which is essential for skeletal muscle repair. Although increasing evidence has confirmed the role of CXCR4/SDF1 in embryonic muscle development, the function of this pathway during adult myogenesis remains to be fully elucidated. In addition, a role for CXCR4 signaling in muscle maintenance and repair has only recently emerged. Here, we have demonstrated that CXCR4 and stromal cell-derived factor-1 (SDF1) are up-regulated in injured muscle, suggesting their involvement in the repair process. In addition, we found that notexin-damaged muscles showed delayed muscle regeneration on treatment with CXCR4 agonist (AMD3100). Accordingly, small-interfering RNA-mediated silencing of SDF1 or CXCR4 in injured muscles impaired muscle regeneration, whereas the addition of SDF1 ligand accelerated repair. Furthermore, we identified that CXCR4/SDF1-regulated muscle repair was dependent on matrix metalloproteinase-10 (MMP-10) activity. Thus, our findings support a model in which MMP-10 activity modulates CXCR4/SDF1 signaling, which is essential for efficient skeletal muscle regeneration.
authors.affiliation: 1 Cell Therapy Area, Division of Cancer, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain .
authors.forename: Miriam
authors.initials: M
authors.lastname: Bobadilla
authors.forename: Neira
authors.initials: N
authors.lastname: Sainz
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Josune
authors.initials: J
authors.lastname: Orbe
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Páramo
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez-Ruiz
mesh_terms: D000818:Animals; D001596:Benzylamines; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D000080027:Cyclams; D004546:Elapid Venoms / Q000633:toxicity; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000293:injuries; D019718:Receptors, CXCR4 / Q000819:agonists / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D000080027:Cyclams; D004546:Elapid Venoms; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C005082:notexin; D053506:Matrix Metalloproteinase 10; C088327:plerixafor