Vasopressin and insulin-like growth factors synergistically induce myogenesis in serum-free medium.
Terminal differentiation of myogenic cells has long been known to be positively regulated by insulin-like growth factors (IGFs). Arg8-vasopressin (AVP) has been recently reported to potently induce myogenic differentiation. In the present study, the effects and the mechanisms of action of AVP and IGFs on myogenic cells have been investigated under conditions allowing growth and differentiation of myogenic cells in a simple serum-free medium. Under these conditions, L6 and L5 myogenic cells slowly proliferate and do not undergo differentiation (less than 1% fusion up to 7 days). AVP rapidly (2-3 days) and dose-dependently induces the formation of multinucleated myotubes. Creatine kinase activity and myosin accumulation are strongly up-regulated by AVP. Insulin or IGF-I or IGF-II, at concentrations that cause extensive differentiation in serum-containing medium, induces a modest degree of differentiation in serum-free medium. The simultaneous presence of AVP and of one of the IGFs in the synthetic medium induces maximal differentiation of L6, L5, and satellite cells. The expression of both myogenin and Myf-5 is dramatically stimulated by AVP. Our results indicate that AVP induces a significant level of myogenic differentiation in the absence of other factors. Furthermore, they suggest that to express their full myogenic potential, IGFs require the presence of other factors normally present in serum and fully mimicked by AVP. These studies support the conclusion that terminal myogenic differentiation may depend on the presence of differentiation factors rather than the absence of growth factors.
Minotti
S
S
Dipartimento di Istologia ed Embriologia Medica, Università La Sapienza, Rome, Italy.
Scicchitano
B M
BM
Nervi
C
C
Scarpa
S
S
Lucarelli
M
M
Molinaro
M
M
Adamo
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015534:Trans-Activators
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D007328:Insulin; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; C503801:Myog protein, mouse; C503803:Myog protein, rat; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D012333:RNA, Messenger; D015534:Trans-Activators; D001127:Arginine Vasopressin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003402:Creatine Kinase; D009218:Myosins