Myostatin regulates cell survival during C2C12 myogenesis

During the myogenic process in vitro, proliferating myoblasts withdraw irre versible from the cell cycle, acquire an apoptosis-resistant phenotype, and fuse into mature myotubes. The key factor regulating both myocyte cell cyc le exit and viability during this transition is the the cyclin-dependent ki nase inhibitor p21(cip1), Here we show that the expression of myostatin, a TGF-P superfamily member known to act as a negative regulator of muscle gro wth, is upregulated in the course of C2C12 cells myogenesis. We also show t hat transient transfection of C2C12 myobasts with an expression vector enco ding mouse myostatin cDNA efficiently inhibits cell proliferation. Paradoxi cally, myostatin cDNA overexpression also enhances the survival of differen tiating C2C12 myocytes, probably by a mechanism involving, at least in part , upregulation of p21(cip1) mRNA. Our results suggest that myostatin role i n myogenesis is more complex than initially suggested and involves another level of regulation apart from inhibition of myoblast proliferation. (C) 20 01 Academic Press.