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Decorin gene transfer promotes muscle cell differentiation and muscle regeneration

Li, Y and Li, J and Zhu, J and Sun, B and Branca, M and Tang, Y and Foster, W and Xiao, X and Huard, J (2007) Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Molecular Therapy, 15 (9). 1616 - 1622. ISSN 1525-0016

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Abstract

We have shown that decorin, a small leucine-rich proteoglycan, can inhibit transforming growth factor (TGF)-β1 to prevent fibrous scar formation and improve muscle healing after injury. In the decorin-treated muscle, an enhancement of muscle regeneration is observed through histological examination. In this article, we report our determination of whether decorin has a direct effect on myogenic cells' differentiation. Our results indicate that myoblasts genetically engineered to express decorin (CD cells) differentiated into myotubes at a significantly higher rate than did control myoblasts (C2C12). This enhanced differentiation led to the up-regulation of myogenic genes (Myf5, Myf6, MyoD, and myogenin) in CD cells in vitro. We speculate that the higher rate of differentiation exhibited by the CD cells is due to the up-regulation of follistatin, peroxisome-proliferator-activated receptor-gamma co-activator-1α (PGC-1α), p21, and the myogenic genes, and the down-regulation of TGF-β1 and myostatin. Decorin gene transfer in vivo promoted skeletal muscle regeneration and accelerated muscle healing after injury. These results suggest that decorin not only prevents fibrosis but also improves muscle regeneration and repair.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Y
Li, J
Zhu, J
Sun, Bbis3@pitt.eduBIS3
Branca, M
Tang, Yyit3@pitt.eduYIT3
Foster, W
Xiao, X
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 1 September 2007
Date Type: Publication
Journal or Publication Title: Molecular Therapy
Volume: 15
Number: 9
Page Range: 1616 - 1622
DOI or Unique Handle: 10.1038/sj.mt.6300250
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
Refereed: Yes
ISSN: 1525-0016
MeSH Headings: Adenoviridae--genetics; Animals; Blotting, Western; Cell Differentiation--genetics; Cell Differentiation--physiology; Cell Line; Cell Transplantation; Decorin; Extracellular Matrix Proteins--genetics; Extracellular Matrix Proteins--physiology; Female; Fibrosis--therapy; Follistatin--metabolism; Genetic Therapy--methods; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Mice, SCID; Models, Biological; Muscle Fibers, Skeletal--cytology; Muscle Fibers, Skeletal--metabolism; Muscle, Skeletal--metabolism; Muscle, Skeletal--pathology; Myoblasts--cytology; Myoblasts--metabolism; Myoblasts--physiology; Myostatin; Proteoglycans--genetics; Proteoglycans--physiology; Regeneration; Trans-Activators--metabolism; Transcription Factors; Transfection--methods; Transforming Growth Factor beta--metabolism; Transforming Growth Factor beta1--metabolism
PubMed ID: 17609657
Date Deposited: 15 May 2014 20:11
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/21615

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