Myostatin Regulates Cell Survival during C2C12 Myogenesis
- 1 January 2001
- journal article
- Published by Elsevier BV in Biochemical and Biophysical Research Communications
- Vol. 280 (2), 561-566
- https://doi.org/10.1006/bbrc.2000.4159
Abstract
During the myogenic process in vitro, proliferating myoblasts withdraw irreversible from the cell cycle, acquire an apoptosis-resistant phenotype, and fuse into mature myotubes. The key factor regulating both myocyte cell cycle exit and viability during this transition is the the cyclin-dependent kinase inhibitor p21(cip1). Here we show that the expression of myostatin, a TGF-beta superfamily member known to act as a negative regulator of muscle growth, is upregulated in the course of C2C12 cells myogenesis. We also show that transient transfection of C2C12 myobasts with an expression vector encoding mouse myostatin cDNA efficiently inhibits cell proliferation. Paradoxically, myostatin cDNA overexpression also enhances the survival of differentiating C2C12 myocytes, probably by a mechanism involving, at least in part, upregulation of p21(cip1) mRNA. Our results suggest that myostatin role in myogenesis is more complex than initially suggested and involves another level of regulation apart from inhibition of myoblast proliferation.Keywords
This publication has 21 references indexed in Scilit:
- Myostatin, a Negative Regulator of Muscle Growth, Functions by Inhibiting Myoblast ProliferationPublished by Elsevier BV ,2000
- Cell Cycle Withdrawal Promotes Myogenic Induction of Akt, a Positive Modulator of Myocyte SurvivalMolecular and Cellular Biology, 1999
- Double muscling in cattle due to mutations in the myostatin geneProceedings of the National Academy of Sciences of the United States of America, 1997
- Cell cycle exit upon myogenic differentiationCurrent Opinion in Genetics & Development, 1997
- Mutations in myostatin (GDF8) in Double-Muscled Belgian Blue and Piedmontese CattleGenome Research, 1997
- A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattleNature Genetics, 1997
- Regulation of skeletal muscle mass in mice by a new TGF-p superfamily memberNature, 1997
- Resistance to Apoptosis Conferred by Cdk Inhibitors During Myocyte DifferentiationScience, 1996
- p53-Independent Expression of p21 Cip1 in Muscle and Other Terminally Differentiating CellsScience, 1995
- Induction of myoblast proliferation in L6 myoblast cultures by fetal serum of double-muscled and normal cattleJournal of Animal Science, 1993