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Published on: February 12, 2020
Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling
Juulia H Lautaoja1, Satu Pekkala1, Arja Pasternack2
1Faculty of Sport and Health Sciences, Neuromuscular Research Center, University of Jyväskylä, 40014 Jyväskylä, Finland.
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.
Insights
Myostatin
Area of Science:
- Skeletal muscle physiology
- Cell signaling pathways
- Cancer biology
Background:
- Myostatin negatively regulates skeletal muscle mass.
- In vitro models are needed to study myostatin's effects mechanistically.
- Understanding myostatin signaling is crucial for muscle-related research.
Purpose of the Study:
- To investigate myostatin's effects on intracellular signaling in different cell types.
- To compare the responsiveness of murine (C2C12) and human (CHQ) myoblasts/myotubes to myostatin.
- To assess the impact of myostatin and tumorkines on inflammatory pathways.
Main Methods:
- Administration of myostatin to C2C12 and CHQ cells.
- Analysis of canonical and noncanonical signaling pathways.
- Coculture of C2C12 myoblasts with colon cancer cells (C2C12-C26).
Main Results:
- Myostatin's signaling effects were reduced in differentiated C2C12 cells, possibly due to increased follistatin and altered activin receptor ligands.
- CHQ cells maintained responsiveness to myostatin with unaltered follistatin levels.
- Both myostatin and coculture stimulated inflammatory pathways, particularly in C2C12 cells.
Conclusions:
- Myostatin's intracellular signaling effects are cell line- and organism-specific.
- Differentiated C2C12 myotubes are not optimal for studying myostatin's canonical and noncanonical signaling due to altered receptor ligand expression.
- Further research into cell-specific responses to myostatin is warranted.
