title: A role for the Wnt3a/β-catenin signaling pathway in the myogenic program of C2C12 cells.
abstract: The Wnt/β-catenin signaling pathway is a key regulator of embryonic development that was first identified in drosophila. More recent work has suggested a role for this pathway in mammalian, myogenesis but this process remains to be more completely elucidated. The current study was designed to investigate the role of the Wnt3a/β-catenin signaling module in C2C12 cell differentiation and myotube formation. Activation of the Wnt/β-catenin pathway in differentiating myoblasts, using lithium chloride supplementation, increased both the number and size of C2C12 myotubes. On the other hand, pharmacological inhibitors of Wnt/β-catenin signaling (IWR-1, XAV939) resulted in significant decreases in myotube length without affecting their numbers. In separate experiments, a neutralizing antibody to Wnt3a also reduced myotube length without affecting the number of myotubes formed during differentiation. Confocal imaging studies revealed that β-catenin was primarily localized in the cytoplasmic region of undifferentiated myoblasts and differentiation resulted in its enhanced expression in myotubes. Additionally, LiCl treatment resulted in enhanced expression of β-catenin in pre-differentiating myoblast cultures. These data suggest that Wnt3a/β-catenin signaling plays a critical role in C2C12 cell differentiation and provides an appropriate model for elucidating its functions in more detail.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, PO Box 1090, Buies Creek, NC, 27506, USA. abraham@campbell.edu.
authors.forename: S Thomas
authors.initials: ST
authors.lastname: Abraham
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D060509:Wnt3A Protein; D051176:beta Catenin; D038501:Tankyrases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
keywords: C2C12 cells; IWR-1-endo; Myotubes; Skeletal muscle differentiation; Wnt signaling; XAV939; β-Catenin