Muscle Cell News Volume 2.20 | Jun 12 2017

TOP STORY

Antisense Oligonucleotide-Mediated Dnm2 Knockdown Prevents and Reverts Myotubular Myopathy in Mice

Investigators showed that systemic delivery of Dnm2 antisense oligonucleotides (ASOs) into Mtm1 knockout mice efficiently reduces DNM2 protein level in muscle and prevents the myopathy from developing. Systemic ASO injection into severely affected mice lead to reversal of muscle pathology within two weeks. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Lipopolysaccharides Induced Inflammatory Responses and Electrophysiological Dysfunctions in Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes

The authors sought to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide in different concentrations for different times. [Sci Rep] Full Article

Extracellular Matrix Protein Laminin Enhances Mesenchymal Stem Cell (MSC) Paracrine Function through αvβ3/CD61 Integrin to Reduce Cardiomyocyte Apoptosis

Scientists found that placenta-derived multipotent cells (PDMCs) significantly reduced cardiomyocyte apoptosis and reactive oxygen species production through the paracrine factors GRO-α, HGF and IL-8. Moreover, culturing PDMCs on plates coated with laminin, an extracellular matrix protein, resulted in significantly enhanced secretion of all three paracrine factors, which further reduced cardiomyocyte apoptosis. [J Cell Mol Med] Full Article

Deregulated Ca²⁺ Cycling Underlies the Development of Arrhythmia and Heart Disease Due to Mutant Obscurin

To assess the effects of R4344Q in vivo, researchers generated a knock-in mouse model. The expression patterns of sarcomeric and Ca²⁺-cycling proteins were unaltered in sedentary one-year-old knock-in myocardia, with the exception of sarco/endoplasmic reticulum Ca²⁺ adenosine triphosphatase 2 and pentameric phospholamban whose levels were significantly increased and decreased, respectively. Isolated cardiomyocytes from one-year-old knock-in hearts exhibited increased Ca²⁺-transients and Ca²⁺-load in the sarcoplasmic reticulum and faster contractility kinetics. [Sci Adv] Full Article

SKELETAL MUSCLE CELLS

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

The authors showed that the addition of the Nup210 nucleoporin to nuclear pore complexes (NPCs) during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. They showed that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. [Dev Cell] Abstract | Press Release | Graphical Abstract

Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, scientists analyzed Taz in vivo and ex vivo in comparison to Yap. [Stem Cells] Abstract

Dysregulation of Nuclear Receptor COUP-TFII Impairs Skeletal Muscle Development

Researchers generated a mouse model ectopically expressing chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) in myogenic precursors to maintain COUP-TFII activity during myogenesis and found that elevated COUP-TFII activity resulted in inefficient skeletal muscle development. Using in vitro cell culture and in vivo mouse models, they showed that COUP-TFII hinders myogenic development by repressing myoblast fusion. [Sci Rep] Full Article

SMOOTH MUSCLE CELLS

ER Stress Dependent Microparticles Derived from Smooth Muscle Cells Promote Endothelial Dysfunction during Thoracic Aortic Aneurysm and Dissection

The degeneration of vascular smooth muscle cells (SMCs) is one of the key features of thoracic aortic aneurysm and dissection. In vitro assay demonstrated that elevated mechanical stretch stimulated the endoplasmic reticulum (ER) stress response and microparticle production from both SMCs and endothelial cells (ECs) in a time-dependent manner. In vivo, administration of an ER stress inhibitor or knockout of CHOP suppressed both apoptosis of EC and the infiltration of inflammatory cells. [Clin Sci (Lond)] Full Article

Persistent Distention of Colon Damages Interstitial Cells of Cajal through Ca²⁺-ERK-AP-1-miR–34c-SCF Deregulation

Chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic smooth muscle cells and colon specimens from Hirschsprung’s disease patients were used. Scientists showed that stem cell factor (SCF) was clearly decreased in distent colon of mice and patients, and microRNA (miR) array and real-time PCR indicated a concomitant increase of miR–34c in distent colon. [J Cell Mol Med] Full Article

Phenotypic Switching Prevention and Proliferation/Migration Inhibition of Vascular Smooth Muscle Cells by the Ruthenium Nitrosyl Complex trans-[Ru(NO)Cl(cyclam](PF₆)₂

Vascular smooth muscle cell migration and proliferation at sites of vascular injury are both critical steps in the development of intimal hyperplasia. Local delivery of nitric oxide (NO) largely prevents these events. Cell proliferation and migration induced by platelet-derived growth factor type BB were significantly inhibited by trans-[Ru(NO)Cl(cyclam](PF₆)₂. [J Pharm Pharmacol] Abstract

Cardiac Regeneration Strategies: Staying Young at Heart

Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at least in mammals, has poor regenerative potential. This deficiency is attributable to the lack of resident cardiac stem cells, combined with roadblocks that limit adult cardiomyocytes from entering the cell cycle and completing division. Insights for regeneration have recently emerged from studies of animals with an elevated innate capacity for regeneration, the innovation of stem cell and reprogramming technologies, and a clearer understanding of the cardiomyocyte genetic program and key extrinsic signals. [Science] Abstract

The Use of Biologics in the Management of Cardiovascular Diseases

The author focuses on the use of stem cells and non-coding RNA agents to characterize the current status of these agents and describe some of the nuances that have led to the extraordinary interest in them as therapeutic agents. [Curr Opin Pharmacol] Abstract

Visit our reviews page to see a complete list of reviews in the muscle cell research field.

CureDuchenne Continues to Support Research for Duplication Mutations in Duchenne, and with Dr. Flanigan from Nationwide Children’s Hospital with a Coalition of Families Impacted by the Disease

CureDuchenne continues to support Dr. Kevin Flanigan from Nationwide Children’s Hospital duplication 2 mutation research to find a treatment for a rare mutation of Duchenne. CureDuchenne has funded more than $1 million to support this research over the past five years. New funding will support IND-enabling studies to complete pre-clinical data that could lead to human clinical trials in early 2018. [CureDuchenne] Press Release

PTC Therapeutics Announces FDA Advisory Committee Meeting for Ataluren for the Treatment of Nonsense Mutation Dystrophinopathy

PTC Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has notified the company of the tentative scheduling of a Peripheral and Central Nervous Systems Drugs Advisory Committee meeting to review the new drug application for ataluren. Ataluren is an oral, first-in-class, protein restoration therapy for the treatment of nonsense mutation dystrophinopathy, including nonsense Duchenne muscular dystrophy. [PTC Therapeutics, Inc.] Press Release

Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France

The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial

Trump Names Sharpless to Lead U.S. Cancer Institute

President Donald Trump announced his intention to appoint Norman “Ned” Sharpless to be the next director of the National Cancer Institute in Bethesda, Maryland. Sharpless, who is 50 years old, is a physician and currently director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. He also holds an academic appointment at the university’s school of medicine. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Biomaterials & Tissue Engineering
July 23-28, 2017
Holderness, New Hampshire, United States

NEW Gordon Research Conferences: Wnt Signaling
August 6-11, 2017
Stowe, Vermont, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Cardiovascular Physiology (University of Nevada, Reno)

Postdoctoral Position – Genetics and Molecular Biology of Congenital Muscle Diseases (Weill Cornell Medical College in Qatar)

Postdoctoral Research Fellow – Muscular Dystrophy (University of Melbourne)

Postdoctoral Fellow – Diabetes and Heart Disease (University Health Network)

Postdoctoral Fellow – Physiology and Cell Biology (University of Nevada, Reno)

Research Fellow – Cardiovascular Diseases (Mayo Clinic)

Postdoctoral Position(s) – Skeletal Muscle Stem Cells (Inserm)

Postdoctoral Associate – Genetics of Muscular Dystrophy (University of Florida College of Medicine)

Postdoctoral/ Graduate Student Positions – Neuromuscular Diseases (University of Alberta)

PhD Studentship – Experimental Genetic Cardiology (Oslo University Hospital)

Postdoctoral Position(s) – Skeletal and Cardiac Muscle Disease Modeling and Regeneration (Duke University)

Postdoctoral Fellowship – Heart Regeneration (Children’s Hospital Los Angeles – University of Southern California)

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