Decorin Gene Transfer Promotes Muscle Cell Differentiation and Muscle Regenerati

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Mol Ther. 2007 Jul 3

Decorin Gene Transfer Promotes Muscle Cell Differentiation and

Muscle Regeneration.

Li Y, Li J, Zhu J, Sun B, Branca M, Tang Y, W, Xiao X, Huard

J.

[1] 1Stem Cell Research Center, Children's Hospital of Pittsburgh,

Pittsburgh, Pennsylvania, USA [2] 2Department of Orthopaedic

Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA [3]

3Department of Pathology, University of Pittsburgh, Pittsburgh,

Pennsylvania, USA.

We have shown that decorin, a small leucine-rich proteoglycan, can

inhibit transforming growth factor (TGF)-beta1 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-1alpha (PGC-1alpha), p21, and the myogenic genes, and the

down-regulation of TGF-beta1 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.