Today in Skeletal Muscle we publish novel research on congenital muscular dystrophy Type 1A (MDC1A). Soonsang Yoon and colleagues communicate the potential uses of immortalized, clonal lines of human MDC1A myogenic cells, in studies of the pathogenic mechanisms of MDC1A, and the development of therapeutic approaches for the disease.
The use of primary cultures of human MDC1A myogenic cells uncovers two key issues; donor numbers are low and the cells have limited replicative ability. In this research article, the authors demonstrate that immortalized clonal lines not only are more numerous in availability and retain their replicative ability, but they also display a marked increase in caspase activity – a pathological change that is observed in primary cell …
The latest research article published in Skeletal Muscle by lead authors Ken Kikuchi , Eri Taniguchi and colleagues, focuses on Rhabdomyosarcoma, a childhood muscle cancer. Co-author Charles Keller describes the importance of deciphering the exact role of Rb1 in this disease and explains how their study will inform future research on this topic:
“Childhood muscle cancer (rhabdomyosarcoma) can be a devastating disease when invasive or metastatic, and yet being relatively rare its (diverse) developmental origins are only recently being elucidated.” Keller references two recent articles published in Cancer Cell; ‘The not-so-skinny on muscle cancer’ and ‘New Insights into the Origin and the Genetic Basis of Rhabdomyosarcomas’ for further information. “An interesting aspect is that cell-of-origin and …
Just published in Skeletal Muscle is a Commentary article by Levy, Campbell and Glass which discusses a recent publication by Song et al., showing that MG53, a muscle-specific protein, has E3 ubiquitin ligase activity that targets the insulin receptor and insulin receptor substrate 1 for degradation. As MG53-null mice are protected from high-fat diet-induced elevations in body weight, blood pressure, and serum cholesterol and triglyceride levels – the hallmarks of Metabolic Syndrome – it appears that MG53 is a key player in mediating systemic metabolic changes. Conversely, transgenic mice that overexpress MG53 display the hallmarks of metabolic syndrome in the absence of a high-fat diet. This is a particularly unexpected finding, as MG53 had previously been characterized as a …
Murphy Roths Large (MRL) mice are an inbred mouse strain that has enhanced healing. This remarkable ability was first noted by researchers who observed that MRL mice could heal ear hole punch wounds seamlessly – they regenerated cartilage, hair follicles, skin and blood vessels without scarring. Decreased fibrosis, altered inflammatory response, reduced apoptosis, increased proliferation, improved remodeling and enhanced stem cell function have all been suggested to explain the rapid healing of the MRL mice. To further complicate the identification of a mechanism for enhanced healing in these mice, over 40 different genetic loci have been associated with aspects of this unusual phenotype.
In the present study, Heydemann and colleagues bred MRL mice with mice lacking gamma-sarcoglycan, …
Cachexia severely limits therapeutic options in cancer patients, and is thought to cause about 20% of cancer deaths. Skeletal muscle mitochondria are emerging as critical mediators of muscle protein turnover during cancer cachexia. Using the severely cachectic ApcMin/+ mice, White and colleagues examined the role of IL-6 on the regulation of mitochondrial remodeling/dysfunction that precedes muscle proteolysis during cachexia. The authors had previously shown that inhibition of IL-6 signaling can attenuate the progression of cachexia. In the current study, they treated ApcMin/+ mice with an antibody against the IL-6 receptor and reduced the loss of mitochondrial biogenesis and content, compared to vehicle-treated mice. IL-6 inhibition also restored the altered mitochondrial fusion and reduced apoptosis observed in cachectic …
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 …
The start of 2012 marked one year since the launch of Skeletal Muscle. In January 2011, the journal set out to provide a home for the increasing amounts of research being conducted into skeletal muscle – from the genes responsible for muscular dystrophies, to the contribution of skeletal muscle to insulin and fatty acid signalling.
To mark this anniversary, Skeletal Muscle published an Editorial written by the journal’s Editors-in-Chief; Profs David Glass, Kevin Campbell and Michael Rudnicki. The Editorial, which can be read in full here, looks back over a successful first year, with 20 original research articles and 16 reviews being published, as well as the journal’s inclusion in PubMed. In this article, the Editors state “The bottom …
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 …
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.
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.