title: TGF-beta's delay skeletal muscle progenitor cell differentiation in an isoform-independent manner.
abstract: Satellite cells are a quiescent heterogeneous population of mononuclear stem and progenitor cells which, once activated, differentiate into myotubes and facilitate skeletal muscle repair or growth. The Transforming Growth Factor-beta (TGF-beta) superfamily members are elevated post-injury and their importance in the regulation of myogenesis and wound healing has been demonstrated both in vitro and in vivo. Most studies suggest a negative role for TGF-beta on satellite cell differentiation. However, none have compared the effect of these three isoforms on myogenesis in vitro. This is despite known isoform-specific effects of TGF-beta1, -beta2 and -beta3 on wound repair in other tissues. In the current study we compared the effect of TGF-beta1, -beta2 and -beta3 on proliferation and differentiation of the C2C12 myoblast cell-line. We found that, irrespective of the isoform, TGF-beta increased proliferation of C2C12 cells by changing the cellular localisation of PCNA to promote cell division and prevent cell cycle exit. Concomitantly, TGF-beta1, -beta2 and -beta3 delayed myogenic commitment by increasing MyoD degradation and decreasing myogenin expression. Terminal differentiation, as measured by a decrease in myosin heavy chain (MHC) expression, was also delayed. These results demonstrate that TGF-beta promotes proliferation and delays differentiation of C2C12 myoblasts in an isoform-independent manner.
authors.affiliation: Department of Physiological Sciences, University of Stellenbosch, Private Bag X1, Stellenbosch 7602, South Africa.
authors.forename: Elske J
authors.initials: EJ
authors.lastname: Schabort
authors.forename: Mathilde
authors.initials: M
authors.lastname: van der Merwe
authors.forename: Benjamin
authors.initials: B
authors.lastname: Loos
authors.forename: Frances P
authors.initials: FP
authors.lastname: Moore
authors.forename: Carola U
authors.initials: CU
authors.lastname: Niesler
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020033:Protein Isoforms / Q000494:pharmacology / Q000502:physiology; D021381:Protein Transport; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta