Skeletal Muscle Blog

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 last 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”.

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Posted at 11:02AM Feb 13, 2012 by Laura Winton in General  |  Comments[0]

Dystrophin/dysferlin null mice as useful therapeutic models

It is well known that some forms of muscular dystrophies are caused by mutations in the genes coding for dystrophin and dysferlin – two proteins which both have important roles in the correct functioning of skeletal muscle.

The dystrophin protein is located in the plasma membrane of skeletal muscle, and is an integral part of the dystrophin-glycoprotein complex (DGC). The DGC forms a link between the sarcolemma (the muscle cell membrane) and the cytoskeleton thereby ensuring cell membrane stability and preventing damage during lengthening contractions of the muscle. Dysferlin on the other hand is known to play a critical role in calcium dependent membrane repair. A defect in either protein’s role has a detrimental effect on the muscle.

A new research article published this month in Skeletal Muscle uses dystrophin/dysferlin double knock-out (DKO) mice to look at how muscle pathology in dysferlin-null mice is exacerbated by an additional dystrophin deficiency. DKO mice show increased histopathology, decreased sarcolemmal integrity and severe functional defects. The double deficiency causes more severe muscular dystrophy than dysferlin-deficient or wild type mice, and also results in the mice being physically weaker, suffering from contraction-induced injuries and having a low force production. In addition, onset of the muscle pathology in mice lacking both dystrophin and dysferlin is earlier than in the dysferlin-deficient mice. 

Han et al. reveal that the role dysferlin has in repairing damaged membranes can be unmasked by a dystrophin deficiency. In dystrophin deficient mice, the initial injury caused by lengthening muscle contractions is more severe than in wild type and dysferlin-null mice. Dystrophin deficient mice are however capable of recovery, revealing the presence of an active membrane repair process to restore membrane integrity. Dysferlin mice on the other hand show a poor recovery, as do DKO mice. These results suggest that the DKO mouse model may be useful in the development of therapies designed to treat dysferlinopathies – muscular dystrophies caused by a defect in the function of the dysferlin protein.

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Posted at 04:13PM Dec 06, 2011 by Laura Winton in General  |  Comments[0]

Immortalized human myoblasts as an innovative cellular tool

For years, research into muscle dystrophies has been limited due to the fact that the animal-derived dystrophic cellular models, which are required to carry out the research, have low proliferative capacities. In the latest research published in Skeletal Muscle, Mamchaoui et al. conclude that immortalised cell lines from patients with neuromuscular diseases have a higher proliferative capacity than the animal-derived cells, and would therefore be useful cellular tools in the investigation of neuromuscular disorders.

Read the full article published in Skeletal Muscle here.

Posted at 11:27AM Nov 17, 2011 by Laura Winton in General  |  Comments[0]

A novel role for PPARdelta in satellite cells and postnatal muscle regeneration

Peroxisome proliferator-activated receptors (PPARs) are typically known for their role in development and energy metabolism. In a recent research paper published in Skeletal Muscle, the importance of the receptors in skeletal muscle metabolism and insulin sensitivity regulation is explored, with the results indicating a novel role for PPARs in satellite cells and postnatal muscle regeneration.

Read the full article published in Skeletal Muscle here.

Posted at 11:23AM Nov 17, 2011 by Laura Winton in General  |  Comments[0]

Skeletal Muscle Journal on Pubmed

Skeletal Muscle, a new BioMed Central journal focused on mechanistic studies advancing the understanding of skeletal muscle biology, has now been accepted by the National Library of Medicine for appearance in PubMed, the free citation resource, located at the National Institutes of Health in the United States. 

Cataloging on PubMed was the last step in the formal launching of the journal, which first appeared online in January of this year. The journal has received enthusiastic support from the community of scientists studying skeletal muscle. We hope that in the years to come Skeletal Muscle will be the first choice for high quality papers covering metabolic, developmental, structural and functional studies on this important tissue, under both normal and pathological conditions.

Posted at 01:55PM Aug 01, 2011 by David Glass in General  |  Comments[0]