title: Influence of PDGF-BB on proliferation and transition through the MyoD-myogenin-MEF2A expression program during myogenesis in mouse C2 myoblasts.
abstract: We have previously demonstrated that PDGF-BB enhances proliferation of C2 myoblasts. This has led us to examine whether the mitogenic influence of PDGF-BB in the C2 model correlates with modulation of specific steps associated with myogenic differentiation. C2 myoblasts transiting through these differentiation specific steps were monitored via immunocytochemistry. We show that the influence of PDGF on enhancing cell proliferation correlates with a delay in the emergence of cells positive for sarcomeric myosin. We further monitored the influence of PDGF-BB on differentiation steps preceding the emergence of myosin+ cells. We demonstrate that mononucleated C2 cells first express MyoD (MyoD+/myogenin- cells) and subsequently, myogenin. Cells negative for both MyoD and myogenin (the phenotype preceding the MyoD+ state) were present at all times in culture and comprised the majority, if not all, of the cells which responded mitogenically to PDGF. Additionally, the frequency of the MyoD+/myogenin+ cell phenotype was reduced in cultures receiving PDGF, suggesting that PDGF can modulate the transition of the cells into the myogenin+ state. We determined that many of the myogenin+ cells subsequently become MEF2A+ and this phenomenon is not influenced by PDGF-BB. FGF-2 also enhanced the proliferation of C2 myoblasts and suppressed the appearance of the myogenin+ cells, but did not influence the subsequent transition into the MEF2A+ state. The study raises the possibility that PDGF-BB and FGF-2 might delay the transition of the C2 cells into the MyoD+/myogenin+ state by depressing a paracrine signal that enhances differentiation.
authors.affiliation: Department of Biological Structure, School of Medicine, University of Washington, Seattle 98195, USA. reuveni@u.washington.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Yablonka-Reuveni
authors.forename: A J
authors.initials: AJ
authors.lastname: Rivera
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D019925:Cyclin A / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis*; D003893:Desmin / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D064326:MEF2 Transcription Factors; D051379:Mice; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D017570:MyoD Protein / Q000032:analysis*; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000032:analysis*; D009218:Myosins / Q000032:analysis; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D019925:Cyclin A; D004268:DNA-Binding Proteins; D003893:Desmin; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D009218:Myosins; D001973:Bromodeoxyuridine