Activated beta-catenin induces myogenesis and inhibits adipogenesis in BM-derived mesenchymal stromal cells.
BACKGROUND
Mesenchymal stromal cells (MSC) have been thought to be attractive candidates for the treatment of degenerative muscle diseases. However, little is known about the molecular mechanisms governing the myogenic differentiation in MSC. As the Wnt signaling pathway has been associated with myogenesis in embryogenesis and post-natal muscle regeneration, we hypothesized that the Wnt signaling pathway may be involved in governing the myogenic differentiation in MSC.


METHODS
Primary MSC were isolated from Sprague-Dawley rats and expanded in proliferation medium. The rMSC were transfected with a constitutively active hbeta-catenin (S37A) plasmid or control vector by Lipofectamine followed by G418 selection. The transfected rMSC were grown to 80% confluence and then cultured in myogenic or adipogenic differentiation medium. Cells were characterized by light microscopy, immunofluorescence and RT-PCR at different time points after myogenic or adipogenic introduction.


RESULTS
Ectopic expression of activated beta-catenin located primarily in the nucleus and activated transcription in rMSC. Overexpression of stabilized beta-catenin induced 27.1 +/- 3.91% rMSC forming long multinucleated cells expressing MyoD, myogenin, desmin and myosin heavy chain (MHC) via evoking the expression of skeletal muscle-specific transcription factors. In addition, overexpression of activated beta-catenin inhibited the adipogenic differentiation in rMSC through down-regulated expressions of C/EBPalpha and PPARgamma.


CONCLUSIONS
To our knowledge, this is the first evidence that activated beta-catenin can induce myogenic differentiation in rMSC. The ability of stabilized beta-catenin to induce myogenic differentiation in rMSC may allow for its therapeutic application.
Shang
Y  C
Y
Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
Zhang
C
C
Wang
S  H
S
Xiong
F
F
Zhao
C  P
C
Peng
F  N
F
Feng
S  W
S
Yu
M  J
M
Li
M  S
M
Zhang
Y  N
Y
D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000302:isolation & purification / Q000378:metabolism*
D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D047495:PPAR gamma; D051153:Wnt Proteins; D051176:beta Catenin