L6E9 myoblasts are deficient of myostatin and additional TGF-beta members are candidates to developmentally control their fiber formation.
This work provides evidence that the robust myoblast differentiation observed in L6E9 cells is causally linked to deficiency of myostatin, which, conversely, has been found to be expressed in C2C12 cells. However, despite the absence of endogenous myostatin, L6E9 myoblasts expressed functional Activin receptors type II (ActRIIs) and follistatin as well as the highly related TGF-beta members Activins and GDF11, suggesting that in this cell line the regulation of fiber size might be under the control of multiple regulators regardless of myostatin. In line with this hypothesis, delivery of a dominant-negative ActRIIb form or the increase of follistatin, as obtained via Trichostatin treatment or stable transfection of a short human follistatin form, enhanced the L6E9 cell differentiation and further increased the size of myotubes, suggesting that L6E9 myoblasts provide a spontaneous myostatin knock-out in vitro model to study TGF-beta ligands involved in developmental regulation of fiber size.
Rossi
Stefania
S
Unit of Biochemistry, Department of Biomedical Sciences and Biotechnologies, University of Brescia, viale Europa 11, 25123 Brescia, Italy.
Stoppani
Elena
E
Gobbo
Massimiliano
M
Caroli
Anna
A
Fanzani
Alessandro
A
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006651:Histocytochemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D055435:Myostatin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D038681:Follistatin; D055435:Myostatin; D016212:Transforming Growth Factor beta; D030301:Activin Receptors, Type II
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