Canonical Wnt signaling is involved in switching from cell proliferation to myogenic differentiation of mouse myoblast cells
Open accessAbstract
BACKGROUND: Wnt/β-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. In addition, Wnt3a and β-catenin are required for muscle-specific gene transcription in embryonic carcinoma cells and satellite-cell proliferation during adult skeletal muscle regeneration. Downstream targets of canonical Wnt signaling are cyclin D1 and c-myc. However both target genes are suppressed during differentiation of mouse myoblast cells, C2C12. Underlying molecular mechanisms of β-catenin signaling during myogenic differentiation remain unknown. RESULTS: Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. We confirmed that several Wnt signaling components, including Wnt9a, Sfrp2 and porcupine, were consistently upregulated in differentiating C2C12 cells. Troponin T-positive myotubes were decreased by Wnt3a overexpression, but not Wnt4. TOP/FOP reporter assays revealed that co-expression with Wnt4 reduced Wnt3a-induced luciferase activity, suggesting that Wnt4 signaling counteracted Wnt3a signaling in myoblasts. FH535, a small-molecule inhibitor of β-catenin/Tcf complex formation, reduced basal β-catenin in the cytoplasm and decreased myoblast proliferation. K252a, a protein kinase inhibitor, increased both cytosolic and membrane-bound β-catenin and enhanced myoblast fusion. Treatments with K252a or Wnt4 resulted in increased cytoplasmic vesicles containing phosphorylated β-catenin (Tyr654) during myogenic differentiation. CONCLUSIONS: These results suggest that various Wnt ligands control subcellular β-catenin localization, which regulate myoblast proliferation and myotube formation. Wnt signaling via β-catenin likely acts as a molecular switch that regulates the transition from cell proliferation to myogenic differentiation.
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Bioinformatic analyses revealed that predicted target genes of differentially expressed miRNAs between ELV-MB and ELV-MT were mainly involved in the control of signaling pathways, and particularly the Wnt signaling pathway known to be regulated during myogenesis.
“Bioinformatic analyses revealed that predicted target genes of differentially expressed miRNAs between ELV-MB and ELV-MT were mainly involved in the control of signaling pathways, and particularly the Wnt signaling pathway known to be regulated during myogenesis (Tanaka et al., 2011).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Tanaka et al., 2011
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- Authors
- Tanaka, S., Terada, K., & Nohno, T.
- Affiliations
- Kawasaki Medical School (JP)
- Corresponding author
- Nohno, Tsutomu
- Venue
- Journal of Molecular Signaling
- Publisher
- Journal of Molecular Signaling
- Published
- 2011-10-05
- Volume
- 6
- Pages
- 12
- ISSN
- 1750-2187 (ISSN-L)
- PMC
- PMC3198762
- OpenAlex
- W2142673125
- Cited by
- 124
- References
- 39
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 13 · 2017: 12 · 2016: 16 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 7
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Journal of Molecular Signaling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Journal of Molecular Signaling (University of Oklahoma Health Sciences Center) (submittedVersion, cc-by)
- Funders
- Ministry of Health, Labour and Welfare
- Kawasaki Medical School (23590227)
- Japan Society for the Promotion of Science (21102, 23590227)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt/β-catenin signaling, β-catenin, myogenesis, myoblast proliferation, C2C12 myoblasts, Wnt3a, Wnt4, Wnt9a, SFRP2, porcupines, β-catenin phosphorylation, myotube formation, myoblast fusion, FH535, K252a, skeletal muscle development
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