Inflammatory cytokines have a negative effect on myoblast differentiation

Myoblast
differentiation is a
process that is required for the regeneration of myofibres post injury. In old
age this is impaired and contributes to the onset of sarcopenia, and the
resulting loss of muscle mass and strength. 

A research paper
published this week in Skeletal
Muscle
explores the effects
of IL-1α and TNF-α on myotube differentiation, and the signalling cascades
through which they act. Despite the ongoing debate into whether
pro-inflammatory cytokines have a positive or negative effect on muscle cell
differentiation, the results from this article clearly demonstrate the
anti-differentiation effects of IL-1α and TNF-α.

Trendelenburg
et al. show that human myoblasts treated with IL-1α and TNF-α induce
Activin A de novo synthesis via the TAK-1/p38/NFκB pathway. TAK-1 and
p38 are both required for Activin A induction – with the inhibition of TAK-1
blocking both the increase in Activin A and the downstream activation of p38,
and the inhibition of p38 resulting in increased differentiation. NFκB also contributes
to Activin A induction, though inhibition of NFκB is less effective than
inhibition of p38 in rescuing myoblast differentiation. This induction of
Activin A then results in the activation of downstream Activin receptor
signalling via SMAD2/3 transcription factors, and the inhibition of myoblast
differentiation.

“This study establishes
the mechanism for an additional anti-muscle effect of cytokines – the blockade
of differentiation by Activin A secretion” explain the authors. “The induction of Activin A by TNF-α and IL-1α may help
to explain some of the phenotypes previously reported in aging animals,
including humans”.

Visit the Skeletal
Muscle
homepage
to read the article in full.

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