Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling
Lautaoja, J. H., Pekkala, S., Pasternack, A., Laitinen, M., Ritvos, O., & Hulmi, J. J. (2020). Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling. Biomolecules, 10(5), Article 695. https://doi.org/10.3390/biom10050695
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Alongside in vivo models, a simpler and more mechanistic approach is required to study the effects of myostatin on skeletal muscle because myostatin is an important negative regulator of muscle size. In this study, myostatin was administered to murine (C2C12) and human (CHQ) myoblasts and myotubes. Canonical and noncanonical signaling downstream to myostatin, related ligands, and their receptor were analyzed. The effects of tumorkines were analyzed after coculture of C2C12 and colon cancer-C26 cells. The effects of myostatin on canonical and noncanonical signaling were strongly reduced in C2C12 cells after differentiation. This may be explained by increased follistatin, an endogenous blocker of myostatin and altered expression of activin receptor ligands. In contrast, CHQ cells were equally responsive to myostatin, and follistatin remained unaltered. Both myostatin administration and the coculture stimulated pathways associated with inflammation, especially in C2C12 cells. In conclusion, the effects of myostatin on intracellular signaling may be cell line- or organism-specific, and C2C12 myotubes seem to be a nonoptimal in vitro model for investigating the effects of myostatin on canonical and noncanonical signaling in skeletal muscle. This may be due to altered expression of activin receptor ligands and their regulators during muscle cell differentiation. ...
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- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Research post as Academy Research Fellow, AoF
Additional information about fundingThis work was funded by the Academy of Finland (Grant No. 308042 to S.P. and 275922 to J.J.H.).
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