title: MMP-10 is required for efficient muscle regeneration in mouse models of injury and muscular dystrophy.
abstract: Matrix metalloproteinases (MMPs), a family of endopeptidases that are involved in the degradation of extracellular matrix components, have been implicated in skeletal muscle regeneration. Among the MMPs, MMP-2 and MMP-9 are upregulated in Duchenne muscular dystrophy (DMD), a fatal X-linked muscle disorder. However, inhibition or overexpression of specific MMPs in a mouse model of DMD (mdx) has yielded mixed results regarding disease progression, depending on the MMP studied. Here, we have examined the role of MMP-10 in muscle regeneration during injury and muscular dystrophy. We found that skeletal muscle increases MMP-10 protein expression in response to damage (notexin) or disease (mdx mice), suggesting its role in muscle regeneration. In addition, we found that MMP-10-deficient muscles displayed impaired recruitment of endothelial cells, reduced levels of extracellular matrix proteins, diminished collagen deposition, and decreased fiber size, which collectively contributed to delayed muscle regeneration after injury. Also, MMP-10 knockout in mdx mice led to a deteriorated dystrophic phenotype. Moreover, MMP-10 mRNA silencing in injured muscles (wild-type and mdx) reduced muscle regeneration, while addition of recombinant human MMP-10 accelerated muscle repair, suggesting that MMP-10 is required for efficient muscle regeneration. Furthermore, our data suggest that MMP-10-mediated muscle repair is associated with VEGF/Akt signaling. Thus, our findings indicate that MMP-10 is critical for skeletal muscle maintenance and regeneration during injury and disease.
authors.affiliation: Cell Therapy Area, Division of Cancer, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Míriam
authors.initials: M
authors.lastname: Bobadilla
authors.forename: Neira
authors.initials: N
authors.lastname: Sáinz
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Josune
authors.initials: J
authors.lastname: Orbe
authors.forename: Alba
authors.initials: A
authors.lastname: de Martino
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García Verdugo
authors.forename: José A
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; D004195:Disease Models, Animal; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*
chemical_list: D053506:Matrix Metalloproteinase 10; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Matrix metalloproteinase-10; Muscle regeneration; Notexin; Satellite cells