title: Matrix metalloproteinase inhibition negatively affects muscle stem cell behavior.
abstract: Skeletal muscle is a large and complex system that is crucial for structural support, movement and function. When injured, the repair of skeletal muscle undergoes three phases: inflammation and degeneration, regeneration and fibrosis formation in severe injuries. During fibrosis formation, muscle healing is impaired because of the accumulation of excess collagen. A group of zinc-dependent endopeptidases that have been found to aid in the repair of skeletal muscle are matrix metalloproteinases (MMPs). MMPs are able to assist in tissue remodeling through the regulation of extracellular matrix (ECM) components, as well as contributing to cell migration, proliferation, differentiation and angiogenesis. In the present study, the effect of GM6001, a broad-spectrum MMP inhibitor, on muscle-derived stem cells (MDSCs) is investigated. We find that MMP inhibition negatively impacts skeletal muscle healing by impairing MDSCs in migratory and multiple differentiation abilities. These results indicate that MMP signaling plays an essential role in the wound healing of muscle tissue because their inhibition is detrimental to stem cells residing in skeletal muscle.
authors: Department of Bioengineering, University of Pittsburgh, PA, USA.
authors: Ian
authors: I
authors: Bellayr
authors: Kyle
authors: K
authors: Holden
authors: Xiaodong
authors: X
authors: Mu
authors: Haiying
authors: H
authors: Pan
authors: Yong
authors: Y
authors: Li
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D020782:Matrix Metalloproteinases
keywords: MMPs; Skeletal muscle stem cells; cell migration; differentiation