A1 Journal article (refereed)
Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling (2020)

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

JYU authors or editors

Publication details

All authors or editors: Lautaoja, Juulia H.; Pekkala, Satu; Pasternack, Arja; Laitinen, Mika; Ritvos, Olli; Hulmi, Juha J.

Journal or series: Biomolecules

eISSN: 2218-273X

Publication year: 2020

Volume: 10

Issue number: 5

Article number: 695

Publisher: MDPI

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/biom10050695

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/68893

Abstract

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.

Keywords: muscles; muscle cells; cell signaling; proteins

Free keywords: coculture; follistatin; inflammation; MAPK; myotube; skeletal muscle; Smad; tumorkine

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Ministry reporting: Yes

Reporting Year: 2020

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