title: Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration.
abstract: Efficient skeletal muscle repair and regeneration require coordinated remodeling of the extracellular matrix (ECM). Previous reports have indicated that matrix metalloproteinases (MMPs) play the pivotal role in ECM remodeling during muscle regeneration. The goal of the current study was to determine if the interstitial collagenase MMP-13 was involved in the muscle repair process. Using intramuscular cardiotoxin injections to induce acute muscle injury, we found that MMP-13 expression and activity transiently increased during the regeneration process. In addition, in muscles from mdx mice, which exhibit chronic injury, MMP-13 expression and protein levels were elevated. In differentiating C2C12 cells, a murine myoblast cell line, Mmp13 expression was most pronounced after myoblast fusion and during myotube formation. Using pharmacological inhibition of MMP-13 to test whether MMP-13 activity is necessary for the proliferation, differentiation, migration, and fusion of C2C12 cells, we found a dramatic blockade of myoblast migration, as well as a delay in differentiation. In contrast, C2C12 cells with stable overexpression of MMP-13 showed enhanced migration, without affecting myoblast maturation. Taken together, these results support a primary role for MMP-13 in myoblast migration that leads to secondary effects on differentiation.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hanqin
authors.initials: H
authors.lastname: Lei
authors.forename: Dephne
authors.initials: D
authors.lastname: Leong
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Smith
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D015870:Gene Expression; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000293:injuries; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012038:Regeneration / Q000502:physiology*
chemical_list: D004179:Cobra Cardiotoxin Proteins; D061965:Matrix Metalloproteinase Inhibitors; D053509:Matrix Metalloproteinase 13
keywords: collagenase; matrix metalloproteinase; muscle repair; myoblast maturation