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Int J Clin Exp Pathol 2013;6(2):124-141
Original Article
Matrix metalloproteinase inhibition negatively affects
muscle stem cell behavior
Ian Bellayr, Kyle Holden, Xiaodong Mu, Haiying Pan, Yong Li
Department of Bioengineering, University of Pittsburgh, PA, USA; Department of Pediatrics, Children’s Hospital
of UMPC, University of Pittsburgh, PA, USA; Department of Orthopaedic Surgery, University of Pittsburgh, School
of Medicine, PA, USA; Department of Pediatric Surgery, University of Texas, School of Medicine at Houston, TX,
USA; The Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine
(IMM) at the University of Texas Health Science Center at Houston, TX, USA
Received November 8, 2012; Accepted November 27, 2012; Epub January 15, 2013; Published February 1, 2013
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. (IJCEP1211010).
Keywords: Skeletal muscle stem cells, MMPs, differentiation, cell migration
Address all correspondence to:
Dr. Yong Li
Children’s Regeneration Medicine
Department of Pediatric Surgery
University of Texas, School of Medicine
1825 Pressler Street, SRB630C
Houston, TX 77030, USA.
Phone: 713-5002438; Fax: 713-5002424
E-mail: yong.li.l@uth.tmc.edu
Original Article
Matrix metalloproteinase inhibition negatively affects
muscle stem cell behavior
Ian Bellayr, Kyle Holden, Xiaodong Mu, Haiying Pan, Yong Li
Department of Bioengineering, University of Pittsburgh, PA, USA; Department of Pediatrics, Children’s Hospital
of UMPC, University of Pittsburgh, PA, USA; Department of Orthopaedic Surgery, University of Pittsburgh, School
of Medicine, PA, USA; Department of Pediatric Surgery, University of Texas, School of Medicine at Houston, TX,
USA; The Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine
(IMM) at the University of Texas Health Science Center at Houston, TX, USA
Received November 8, 2012; Accepted November 27, 2012; Epub January 15, 2013; Published February 1, 2013
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. (IJCEP1211010).
Keywords: Skeletal muscle stem cells, MMPs, differentiation, cell migration
Address all correspondence to:
Dr. Yong Li
Children’s Regeneration Medicine
Department of Pediatric Surgery
University of Texas, School of Medicine
1825 Pressler Street, SRB630C
Houston, TX 77030, USA.
Phone: 713-5002438; Fax: 713-5002424
E-mail: yong.li.l@uth.tmc.edu
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