microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice

Liu, Ning; Williams, Andrew H; Maxeiner, Johanna M.; Bezprozvannaya, Svetlana; Shelton, John M.; Richardson, James A.; Bassel‐Duby, Rhonda; Olson, Eric N.

doi:10.1172/jci62656

Cited by 302 publications

(335 citation statements)

References 56 publications

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“…The role of miRs is essential to many important cell processes, such as proliferation, differentiation, and apoptosis (37); therefore, expression levels of these three specific miRs can be used to track development of skeletal muscle as it matures from skeletal myoblasts. MiR-1 and miR-206 promote myoblast differentiation, while miR133a promotes proliferation (10,11,21,37). Permutation of the ratios of these miRs can lead to various developmental and functional alterations, including damaged sarcomere organization and impaired contractile function of cardiac muscle in miR-1-overexpressing mice (1) and delayed formation of new neuromuscular junctions after nerve injury in miR-206-knockout mice (6, 39).…”

mentioning

confidence: 99%

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro

Cheng

El-Abd

Bui

et al. 2014

American Journal of Physiology-Cell Physiology

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Conditions under which skeletal myoblasts are cultured in vitro are critical to growth and differentiation of these cells into mature skeletal myofibers. We examined several culture conditions that promoted human skeletal myoblast (HSkM) culture and examined the effect of microRNAs and mechanical stimulation on differentiation. Culture conditions for HSkM are different from those that enable rapid C2C12 myoblast differentiation. Culture on a growth factor-reduced Matrigel (GFR-MG)-coated surface in 2% equine serum-supplemented differentiation medium to promote HSkM differentiation under static conditions was compared with culture conditions used for C2C12 cell differentiation. Such conditions led to a Ͼ20-fold increase in myogenic miR-1, miR-133a, and miR-206 expression, a Ͼ2-fold increase in myogenic transcription factor Mef-2C expression, and an increase in sarcomeric ␣-actinin protein. Imposing Ϯ10% cyclic stretch at 0.5 Hz for 1 h followed by 5 h of rest over 2 wk produced a Ͼ20% increase in miR-1, miR-133a, and miR-206 expression in 8% equine serum and a Ͼ35% decrease in 2% equine serum relative to static conditions. HSkM differentiation was accelerated in vitro by inhibition of proliferationpromoting miR-133a: immunofluorescence for sarcomeric ␣-actinin exhibited accelerated development of striations compared with the corresponding negative control, and Western blotting showed 30% more ␣-actinin at day 6 postdifferentiation. This study showed that 100 g/ml GFR-MG coating and 2% equine serum-supplemented differentiation medium enhanced HSkM differentiation and myogenic miR expression and that addition of antisense miR-133a alone can accelerate primary human skeletal muscle differentiation in vitro. skeletal muscle; microRNA; myogenesis; differentiation; tissue engineering THE DYNAMICS OF PRIMARY HUMAN skeletal myoblast (HSkM) growth and differentiation into mature myofibers are critical to their use for applications in regenerative medicine, such as repair of severe muscle injuries, congenital defects, and muscular dystrophy. Most studies have focused on rodent myoblasts, and the bulk of the research has been carried out with the widely used immortalized murine C2C12 myoblast line, which is used for ease of culture, differentiation potential, and accessibility (7). Culture conditions for these cells have been optimized to ensure rapid growth and effective differentiation in vitro. These cells do not require protein-coated substrates and differentiate well in a range of equine serum-supplemented differentiation media (DM) (14,24,28,29,32). While C2C12 cells have provided invaluable information about key mechanistic steps in differentiation (31), extensive in vitro cultivation may lead to deviations from normal biological processes that are important for differentiation of myoblasts in a normal in vivo environment. Less is known about the dynamics of key differentiation factors in primary human myoblasts and how culture conditions affect the changes in these factors (3).In vitro, rodent myoblast differentiati...

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confidence: 99%

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro

Cheng

El-Abd

Bui

et al. 2014

American Journal of Physiology-Cell Physiology

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“…Histone acetyltransferases and deacetylases are critical enzymes affecting a variety of genes involved in muscle wasting by modulating satellite cell activation and differentiation [41]. A recent study of satellite cell activation identified a metabolic switch from fatty acid oxidation to glycolysis, thus decreasing histone deacetylase SIRT1 activity [34]. This switch resulted in increased H4K16 acetylation and initiation of muscle gene expression.…”

Section: Epigenetic Control Of Muscle Catabolismmentioning

confidence: 99%

“…Unlike the cytotoxic effect chemotherapy regimens, the effect of epigenetic treatments is aimed to modify phenotypes by reprogramming gene expression. Thus, understanding epigenetic regulation of cancer-associated muscle catabolism will aid development of therapeutic strategies designed to prevent or reverse muscle wasting, thereby improving overall survival and quality of life for cancer cachexia patients [30,34,42,46].…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Epigenetics of cancer-associated muscle catabolism

et al. 2017

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Cancer patients are commonly affected by cachexia, a wasting process involving muscle and fat. Specifically, loss of the muscle compartment has been associated with poor prognosis and suboptimal response to therapy. Nutritional support has been ineffective in treating this process leading to investigations into the underlying molecular processes governing muscle catabolism. In this commentary, we discuss the molecular mechanisms of cancer-associated muscle metabolism and the epigenetic processes responsible for the muscle wasting phenotype. Ultimately, we highlight how the epigenome may serve as a promising therapeutic target in reversing cancer-associated muscle catabolism.

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“…Once SCs differentiate, miR-128a, miR-1 and miR-206 cooperate to block cell proliferation by inhibiting the expression of several targets in the insulin signaling pathway and Pax7 expression [87,88] . Indeed, the loss of miR-1 and miR-206 increases Pax7 expression, enhances SC proliferation and significantly inhibits myoblast differentiation [87,89] . The inhibition of cell proliferation is also achieved via the downregulation of the Ccnd1 gene by both miR-26a and miR-1 [90] .…”

Section: Epigenetic Control Of Sc Differentiationmentioning

confidence: 99%

“…In addition, miR-133a and miR-133b inhibit cell proliferation and promote myoblast differentiation by negatively regulating the FGFR1 and PP2AC proteins, which participate in ERK1/2-mediated signal transduction [91] . In addition to inhibiting Pax7, miR-206 promotes SC differentiation and fusion to muscle fibers via the suppression of a collection of negative regulators of myogenesis, such as notch3, igfbp5, Meox2, RARB, Fzd7, MAP4K3, CLCN3, and NFAT5 [89,92] . An important role in determining SC lineage commitment has been attributed to miR-133 [93] .…”

Section: Epigenetic Control Of Sc Differentiationmentioning

confidence: 99%

New insights into the epigenetic control of satellite cells

Moresi

Marroncelli

Adamo

2015

WJSC

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Epigenetics finely tunes gene expression at a functional level without modifying the DNA sequence, thereby contributing to the complexity of genomic regulation. Satellite cells (SCs) are adult muscle stem cells that are important for skeletal post-natal muscle growth, homeostasis and repair. The understanding of the epigenome of SCs at different stages and of the multiple layers of the post-transcriptional regulation of gene expression is constantly expanding. Dynamic interactions between different epigenetic mechanisms regulate the appropriate timing of muscle-specific gene expression and influence the lineage fate of SCs. In this review, we report and discuss the recent literature about the epigenetic control of SCs during the myogenic process from activation to proliferation and from their commitment to a muscle cell fate to their differentiation and fusion to myotubes. We describe how the coordinated activities of the histone methyltransferase families Polycomb group (PcG), which represses the expression of developmentally regulated genes, and Trithorax group, which antagonizes the repressive activity of the PcG, regulate myogenesis by restricting gene expression in a time-dependent manner during each step of the process. We discuss how histone acetylation and deacetylation occurs in specific loci throughout SC differentiation to enable the time-dependent transcription of specific genes. Moreover, we describe the multiple roles of microRNA, an additional epigenetic mechanism, in regulating gene expression in SCs, by repressing or enhancing gene transcription or translation during each step of myogenesis. The importance of these epigenetic pathways in modulating SC activation and differentiation renders them as promising targets for disease interventions. Understanding the most recent findings regarding the epigenetic mechanisms that regulate SC behavior is useful from the perspective of pharmacological manipulation for improving muscle regeneration and for promoting muscle homeostasis under pathological conditions.

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microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice

Cited by 302 publications

References 56 publications

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro

Epigenetics of cancer-associated muscle catabolism

New insights into the epigenetic control of satellite cells

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