Articles

Alterations to mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism

The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects...

Authors: Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac and Markus A. Rüegg

Chromatin-wide and transcriptome profiling integration uncovers p38α MAPK as a global regulator of skeletal muscle differentiation

Extracellular stimuli induce gene expression responses through intracellular signaling mediators. The p38 signaling pathway is a paradigm of the mitogen-activated protein kinase (MAPK) family that, although or...

Authors: Jessica Segalés, Abul B. M. M. K. Islam, Roshan Kumar, Qi-Cai Liu, Pedro Sousa-Victor, F. Jeffrey Dilworth, Esteban Ballestar, Eusebio Perdiguero and Pura Muñoz-Cánoves

Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway

Hypoxia exposure is known to induce an alteration in skeletal muscle fiber-type distribution mediated by hypoxia-inducible factor (HIF)-α. The downstream pathway of HIF-α leading to fiber-type shift, however, ...

Authors: Junchul Shin, Aki Nunomiya, Yasuo Kitajima, Takashi Dan, Toshio Miyata and Ryoichi Nagatomi

Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts

Studies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftmen...

Authors: Paraskevi Sakellariou, Andrea O’Neill, Amber L. Mueller, Guido Stadler, Woodring E. Wright, Joseph A. Roche and Robert J. Bloch

Attenuated Ca²⁺ release in a mouse model of limb girdle muscular dystrophy 2A

Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 kno...

Authors: Marino DiFranco, Irina Kramerova, Julio L. Vergara and Melissa Jan Spencer

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-...

Authors: Jihee Kim, Mark Hopkinson, Manoli Kavishwar, Marta Fernandez-Fuente and Susan Carol Brown

Failed upregulation of TFAM protein and mitochondrial DNA in oxidatively deficient fibers of chronic obstructive pulmonary disease locomotor muscle

Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary d...

Authors: Yana Konokhova, Sally Spendiff, R. Thomas Jagoe, Sudhakar Aare, Sophia Kapchinsky, Norah J. MacMillan, Paul Rozakis, Martin Picard, Mylène Aubertin-Leheudre, Charlotte H. Pion, Jean Bourbeau, Russell T. Hepple and Tanja Taivassalo

Alternating bipolar field stimulation identifies muscle fibers with defective excitability but maintained local Ca²⁺ signals and contraction

Most cultured enzymatically dissociated adult myofibers exhibit spatially uniform (UNI) contractile responses and Ca²⁺ transients over the entire myofiber in response to electric field stimuli of either polarity ...

Authors: Erick O. Hernández-Ochoa, Camilo Vanegas, Shama R. Iyer, Richard M. Lovering and Martin F. Schneider

Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice

Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with grea...

Authors: Adeel Safdar, Konstantin Khrapko, James M. Flynn, Ayesha Saleem, Michael De Lisio, Adam P. W. Johnston, Yevgenya Kratysberg, Imtiaz A. Samjoo, Yu Kitaoka, Daniel I. Ogborn, Jonathan P. Little, Sandeep Raha, Gianni Parise, Mahmood Akhtar, Bart P. Hettinga, Glenn C. Rowe…

DNA-binding sequence specificity of DUX4

Misexpression of the double homeodomain transcription factor DUX4 results in facioscapulohumeral muscular dystrophy (FSHD). A DNA-binding consensus with two tandem TAAT motifs based on chromatin IP peaks has b...

Authors: Yu Zhang, John K. Lee, Erik A. Toso, Joslynn S. Lee, Si Ho Choi, Matthew Slattery, Hideki Aihara and Michael Kyba

Decrease of myofiber branching via muscle-specific expression of the olfactory receptor mOR23 in dystrophic muscle leads to protection against mechanical stress

Abnormal branched myofibers within skeletal muscles are commonly found in diverse animal models of muscular dystrophy as well as in patients. Branched myofibers from dystrophic mice are more susceptible to bre...

Authors: Christophe Pichavant, Thomas J. Burkholder and Grace K. Pavlath

The ins and outs of muscle stem cell aging

Skeletal muscle has a remarkable capacity to regenerate by virtue of its resident stem cells (satellite cells). This capacity declines with aging, although whether this is due to extrinsic changes in the envir...

Authors: Andrew S. Brack and Pura Muñoz-Cánoves

Genetic disruption of Ano5 in mice does not recapitulate human ANO5-deficient muscular dystrophy

Anoctamin 5 (ANO5) is a member of a conserved gene family (TMEM16), which codes for proteins predicted to have eight transmembrane domains and putative Ca²⁺-activated chloride channel (CaCC) activity. It was rece...

Authors: Jing Xu, Mona El Refaey, Li Xu, Lixia Zhao, Yandi Gao, Kyle Floyd, Tallib Karaze, Paul M. L. Janssen and Renzhi Han

Pervasive satellite cell contribution to uninjured adult muscle fibers

Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident muscle stem cells or satellite cells are required for muscle growth and repair, i...

Authors: Bradley Pawlikowski, Crystal Pulliam, Nicole Dalla Betta, Gabrielle Kardon and Bradley B. Olwin

CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. The immune inflammatory response also contributes to disease progression in DMD patients. In a previous study, we demonstrated h...

Authors: Fernanda Pinto-Mariz, Luciana Rodrigues Carvalho, Alexandra Prufer De Queiroz Campos Araujo, Wallace De Mello, Márcia Gonçalves Ribeiro, Maria Do Carmo Soares Alves Cunha, Pedro Hernan Cabello, Ingo Riederer, Elisa Negroni, Isabelle Desguerre, Mariana Veras, Erica Yada, Yves Allenbach, Olivier Benveniste, Thomas Voit, Vincent Mouly…

Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null mouse

Obese adults are prone to develop metabolic and cardiovascular diseases. Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and car...

Authors: Antonios Matsakas, Domenick A. Prosdocimo, Robert Mitchell, Henry Collins-Hooper, Natasa Giallourou, Jonathan R. Swann, Paul Potter, Thomas Epting, Mukesh K. Jain and Ketan Patel

PAX7 is required for patterning the esophageal musculature

The mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth. In order to better understand the mechanisms that c...

Authors: Daisuke Chihara, Anthony I. Romer, C. Florian Bentzinger, Michael A. Rudnicki and Robert S. Krauss

Elusive sources of variability of dystrophin rescue by exon skipping

Systemic delivery of anti-sense oligonucleotides to Duchenne muscular dystrophy (DMD) patients to induce de novo dystrophin protein expression in muscle (exon skipping) is a promising therapy. Treatment with P...

Authors: Maria Candida Vila, Margaret Benny Klimek, James S. Novak, Sree Rayavarapu, Kitipong Uaesoontrachoon, Jessica F. Boehler, Alyson A. Fiorillo, Marshall W. Hogarth, Aiping Zhang, Conner Shaughnessy, Heather Gordish-Dressman, Umar Burki, Volker Straub, Qi Long Lu, Terence A. Partridge, Kristy J. Brown…

Reduced voluntary running performance is associated with impaired coordination as a result of muscle satellite cell depletion in adult mice

Satellite cells, or muscle stem cells, have been thought to be responsible for all muscle plasticity, but recent studies using genetically modified mouse models that allow for the conditional ablation of satel...

Authors: Janna R. Jackson, Tyler J. Kirby, Christopher S. Fry, Robin L. Cooper, John J. McCarthy, Charlotte A. Peterson and Esther E. Dupont-Versteegden

Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Duchenne muscular dystrophy (DMD) is a devastating X-linked recessive genetic myopathy. DMD physiopathology is still not fully understood and a prenatal onset is suspected but difficult to address.

Authors: Emmanuelle Massouridès, Jérôme Polentes, Philippe-Emmanuel Mangeot, Virginie Mournetas, Juliette Nectoux, Nathalie Deburgrave, Patrick Nusbaum, France Leturcq, Linda Popplewell, George Dickson, Nicolas Wein, Kevin M. Flanigan, Marc Peschanski, Jamel Chelly and Christian Pinset

Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9

Gene therapy strategies are promising therapeutic options for monogenic muscular dystrophies, with several currently underways. The adeno-associated viral (AAV) vector is among the most effective gene delivery...

Authors: Muhammad Riaz, Yotam Raz, Elizabeth B. Moloney, Maaike van Putten, Yvonne D. Krom, Silvere M. van der Maarel, Joost Verhaagen and Vered Raz

Pax3-induced expansion enables the genetic correction of dystrophic satellite cells

Satellite cells (SCs) are indispensable for muscle regeneration and repair; however, due to low frequency in primary muscle and loss of engraftment potential after ex vivo expansion, their use in cell therapy ...

Authors: Antonio Filareto, Fabrizio Rinaldi, Robert W. Arpke, Radbod Darabi, Joseph J. Belanto, Erik A. Toso, Auston Z. Miller, James M. Ervasti, R. Scott McIvor, Michael Kyba and Rita CR Perlingeiro

Genetic characterization and improved genotyping of the dysferlin-deficient mouse strain Dysf ^tm1Kcam

Mouse models of dysferlinopathies are valuable tools with which to investigate the pathomechanisms underlying these diseases and to test novel therapeutic strategies. One such mouse model is the Dysf ...

Authors: Tatiana Wiktorowicz, Jochen Kinter, Kazuhiro Kobuke, Kevin P. Campbell and Michael Sinnreich

A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging

Although high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational com...

Authors: Jing Su, Carl Ekman, Nikolay Oskolkov, Leo Lahti, Kristoffer Ström, Alvis Brazma, Leif Groop, Johan Rung and Ola Hansson

Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice

Loss of skeletal muscle mass and function in humans is associated with significant morbidity and mortality. The role of myostatin as a key negative regulator of skeletal muscle mass and function has supported ...

Authors: Esther Latres, Jeffrey Pangilinan, Lawrence Miloscio, Roy Bauerlein, Erqian Na, Terra B. Potocky, Ying Huang, Mark Eckersdorff, Ashique Rafique, Jason Mastaitis, Calvin Lin, Andrew J. Murphy, George D. Yancopoulos, Jesper Gromada and Trevor Stitt

Skeletal muscle interleukin 15 promotes CD8⁺ T-cell function and autoimmune myositis

Interleukin 15 (IL-15) is thought to be abundant in the skeletal muscle under steady state conditions based on RNA expression; however, the IL-15 RNA level may not reflect the protein level due to post-transcr...

Authors: Po-Lin Huang, Mau-Sheng Hou, Szu-Wen Wang, Chin-Ling Chang, Yae-Huei Liou and Nan-Shih Liao

Erratum to: Increased microenvironment stiffness in damaged myofibers promotes myogenic progenitor cell proliferation

Authors: Frédéric Trensz, Fabrice Lucien, Vanessa Couture, Thomas Söllrald, Geneviève Drouin, André-Jean Rouleau, Claire M. Dubois, Michel Grandbois, Gregory Lacraz and Guillaume Grenier

Syntaxin 4 regulates the surface localization of a promyogenic receptor Cdo thereby promoting myogenic differentiation

Syntaxins are a family of membrane proteins involved in vesicle trafficking, such as synaptic vesicle exocytosis. Syntaxin 4 (Stx4) is expressed highly in skeletal muscle and plays a critical role in insulin-s...

Authors: Miran Yoo, Bok-Geon Kim, Sang-Jin Lee, Hyeon-Ju Jeong, Jong Woo Park, Dong-Wan Seo, Yong Kee Kim, Hoi Young Lee, Jeung-Whan Han, Jong-Sun Kang and Gyu-Un Bae

Mesoangioblast delivery of miniagrin ameliorates murine model of merosin-deficient congenital muscular dystrophy type 1A

Merosin-deficient congenital muscular dystrophy type-1A (MDC1A) is characterized by progressive muscular dystrophy and dysmyelinating neuropathy caused by mutations of the α2 chain of laminin-211, the predomin...

Authors: Teuta Domi, Emanuela Porrello, Daniele Velardo, Alessia Capotondo, Alessandra Biffi, Rossana Tonlorenzi, Stefano Amadio, Alessandro Ambrosi, Yuko Miyagoe-Suzuki, Shin’ichi Takeda, Markus A. Ruegg and Stefano Carlo Previtali

Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype

Transport protein particle (TRAPP) is a multiprotein complex involved in endoplasmic reticulum-to-Golgi trafficking. Zebrafish with a mutation in the TRAPPC11 orthologue showed hepatomegaly with steatosis and def...

Authors: Wen-Chen Liang, Wenhua Zhu, Satomi Mitsuhashi, Satoru Noguchi, Michael Sacher, Megumu Ogawa, Hsiang-Hung Shih, Yuh-Jyh Jong and Ichizo Nishino

GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice

The plasma membranes of striated muscle cells are particularly susceptible to rupture as they endure significant mechanical stress and strain during muscle contraction, and studies have shown that defects in m...

Authors: Kaitlin C. Lenhart, Thomas J. O’Neill IV, Zhaokang Cheng, Rachel Dee, Alexis R. Demonbreun, Jianbin Li, Xiao Xiao, Elizabeth M. McNally, Christopher P. Mack and Joan M. Taylor

Intracellular Ca²⁺-handling differs markedly between intact human muscle fibers and myotubes

In skeletal muscle, intracellular Ca²⁺ is an important regulator of contraction as well as gene expression and metabolic processes. Because of the difficulties to obtain intact human muscle fibers, human myotubes...

Authors: Karl Olsson, Arthur J. Cheng, Seher Alam, Mamdoh Al-Ameri, Eric Rullman, Håkan Westerblad, Johanna T. Lanner, Joseph D. Bruton and Thomas Gustafsson

Upregulated IL-1β in dysferlin-deficient muscle attenuates regeneration by blunting the response to pro-inflammatory macrophages

Loss-of-function mutations in the dysferlin gene (DYSF) result in a family of muscle disorders known collectively as the dysferlinopathies. Dysferlin-deficient muscle is characterized by inflammatory foci and ...

Authors: Tatiana V. Cohen, Gina M. Many, Bryan D. Fleming, Viola F. Gnocchi, Svetlana Ghimbovschi, David M. Mosser, Eric P. Hoffman and Terence A. Partridge

Involvement of adiponectin in the pathogenesis of dystrophinopathy

The hormone adiponectin (ApN) is decreased in the metabolic syndrome, where it plays a key pathogenic role. ApN also exerts some anti-inflammatory effects on skeletal muscles in mice exposed to acute or chroni...

Authors: Michel Abou-Samra, Sophie Lecompte, Olivier Schakman, Laurence Noel, Marie C. Many, Philippe Gailly and Sonia M. Brichard

Regions of ryanodine receptors that influence activation by the dihydropyridine receptor β_1a subunit

Although excitation-contraction (EC) coupling in skeletal muscle relies on physical activation of the skeletal ryanodine receptor (RyR1) Ca²⁺ release channel by dihydropyridine receptors (DHPRs), the activation p...

Authors: Robyn T. Rebbeck, Hermia Willemse, Linda Groom, Marco G. Casarotto, Philip G. Board, Nicole A. Beard, Robert T. Dirksen and Angela F. Dulhunty

Developmental myosins: expression patterns and functional significance

Developing skeletal muscles express unique myosin isoforms, including embryonic and neonatal myosin heavy chains, coded by the myosin heavy chain 3 (MYH3) and MYH8 genes, respectively, and myosin light chain 1 em...

Authors: Stefano Schiaffino, Alberto C. Rossi, Vika Smerdu, Leslie A. Leinwand and Carlo Reggiani

Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay

Myostatin is a protein synthesized and secreted by skeletal muscle that negatively regulates muscle mass. The extent to which circulating myostatin levels change in the context of aging is controversial, large...

Authors: H. Robert Bergen III, Joshua N. Farr, Patrick M. Vanderboom, Elizabeth J. Atkinson, Thomas A. White, Ravinder J. Singh, Sundeep Khosla and Nathan K. LeBrasseur

Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment

In addition to the primary symptoms arising from inflamed joints, muscle weakness is prominent and frequent in patients with rheumatoid arthritis (RA). Here, we investigated the mechanisms of arthritis-induced...

Authors: Takashi Yamada, Masami Abe, Jaesik Lee, Daisuke Tatebayashi, Koichi Himori, Keita Kanzaki, Masanobu Wada, Joseph D. Bruton, Håkan Westerblad and Johanna T. Lanner

A differential response to newt regeneration extract by C2C12 and primary mammalian muscle cells

Dedifferentiation, a process whereby differentiated cells lose their specialized characteristics and revert to a less differentiated state, plays a key role in the regeneration process in urodele amphibians su...

Authors: Sarah Kawesa, Jason Vanstone and Catherine Tsilfidis

Akt-mediated phosphorylation controls the activity of the Y-box protein MSY3 in skeletal muscle

The Y-box protein MSY3/Csda represses myogenin transcription in skeletal muscle by binding a highly conserved cis-acting DNA element located just upstream of the myogenin minimal promoter (myogHCE). It is not ...

Authors: Luciana De Angelis, Sreeram Balasubramanian and Libera Berghella

The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle

Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. Within skeletal muscle exists an intrinsic...

Authors: Brian A Hodge, Yuan Wen, Lance A Riley, Xiping Zhang, Jonathan H England, Brianna D Harfmann, Elizabeth A Schroder and Karyn A Esser

Muscular dystrophy in the mdx mouse is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia

Preclinical testing of potential therapies for Duchenne muscular dystrophy (DMD) is conducted predominantly of the mdx mouse. But lack of a detailed quantitative description of the pathology of this animal limits...

Authors: William Duddy, Stephanie Duguez, Helen Johnston, Tatiana V Cohen, Aditi Phadke, Heather Gordish-Dressman, Kanneboyina Nagaraju, Viola Gnocchi, SiewHui Low and Terence Partridge

A reporter mouse for optical imaging of inflammation in mdx muscles

Duchenne muscular dystrophy (DMD) is due to mutations in the gene coding for human DMD; DMD is characterized by progressive muscle degeneration, inflammation, fat accumulation, and fibrosis. The mdx mouse model o...

Authors: Leonel Martinez, Natalia V Ermolova, Tomo-O Ishikawa, David B Stout, Harvey R Herschman and Melissa J Spencer

The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells

Muscle stem cell transplantation is a possible treatment for muscular dystrophy. In addition to the intrinsic properties of the stem cells, the local and systemic environment plays an important role in determi...

Authors: Jinhong Meng, Maximilien Bencze, Rowan Asfahani, Francesco Muntoni and Jennifer E Morgan

Wnt/β-catenin controls follistatin signalling to regulate satellite cell myogenic potential

Adult skeletal muscle regeneration is a highly orchestrated process involving the activation and proliferation of satellite cells, an adult skeletal muscle stem cell. Activated satellite cells generate a trans...

Authors: Andrew E Jones, Feodor D Price, Fabien Le Grand, Vahab D Soleimani, Sarah A Dick, Lynn A Megeney and Michael A Rudnicki

Effect of levosimendan on the contractility of muscle fibers from nemaline myopathy patients with mutations in the nebulin gene

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is characterized by generalized skeletal muscle weakness, often from birth. To date, no therapy exists that enhances the contractile ...

Authors: Josine M de Winter, Barbara Joureau, Vasco Sequeira, Nigel F Clarke, Jolanda van der Velden, Ger JM Stienen, Henk Granzier, Alan H Beggs and Coen AC Ottenheijm

In vitro stability of therapeutically relevant, internally truncated dystrophins

The X-linked recessive disease Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding the protein dystrophin. Despite its large size, dystrophin is a highly stable protein, demonstrating...

Authors: Jackie L McCourt, Katrina K Rhett, Michele A Jaeger, Joseph J Belanto, Dana M Talsness and James M Ervasti

Oxidative stress, mitochondrial damage, and cores in muscle from calsequestrin-1 knockout mice

Mutations in the gene encoding ryanodine receptor type-1 (RYR1), the calcium ion (Ca ²⁺) release channel in the sarcoplasmic reticulum (SR) of skeletal muscle, are linked to central ...

Authors: Cecilia Paolini, Marco Quarta, Lan Wei-LaPierre, Antonio Michelucci, Alessandra Nori, Carlo Reggiani, Robert T Dirksen and Feliciano Protasi

PGC-1α modulates denervation-induced mitophagy in skeletal muscle

Alterations in skeletal muscle contractile activity necessitate an efficient remodeling mechanism. In particular, mitochondrial turnover is essential for tissue homeostasis during muscle adaptations to chronic...

Authors: Anna Vainshtein, Eric MA Desjardins, Andrea Armani, Marco Sandri and David A Hood

Retinoic acid promotes myogenesis in myoblasts by antagonizing transforming growth factor-beta signaling via C/EBPβ

The effects of transforming growth factor-beta (TGFβ) are mediated by the transcription factors Smad2 and Smad3. During adult skeletal myogenesis, TGFβ signaling inhibits the differentiation of myoblasts, and ...

Authors: Émilie Lamarche, Neena Lala-Tabbert, Angelo Gunanayagam, Catherine St-Louis and Nadine Wiper-Bergeron