Articles

PGC-1α modulates necrosis, inflammatory response, and fibrotic tissue formation in injured skeletal muscle

Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. The peroxisome proliferator-activated receptor γ coactivator 1α (PG...

Authors: Ivana Dinulovic, Regula Furrer, Sabrina Di Fulvio, Arnaud Ferry, Markus Beer and Christoph Handschin

Established cell surface markers efficiently isolate highly overlapping populations of skeletal muscle satellite cells by fluorescence-activated cell sorting

Fluorescent-activated cell sorting (FACS) has enabled the direct isolation of highly enriched skeletal muscle stem cell, or satellite cell, populations from postnatal tissue. Several distinct surface marker pa...

Authors: Claire C. Maesner, Albert E. Almada and Amy J. Wagers

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

Authors: Frédéric Trensz, Fabrice Lucien, Vanessa Couture, Thomas Söllradl, Geneviève Drouin, André-Jean Rouleau, Michel Grandbois, Gregory Lacraz and Guillaume Grenier

Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury

Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of tra...

Authors: Kristy Swiderski, Savant S. Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I. Stapleton, René Koopman and Gordon S. Lynch

The functional significance of the skeletal muscle clock: lessons from Bmal1 knockout models

The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regul...

Authors: Stefano Schiaffino, Bert Blaauw and Kenneth A. Dyar

VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions

Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to a...

Authors: Satoshi Sugita, Leland L. Fleming, Caleb Wood, Sydney K. Vaughan, Matheus P. S. M. Gomes, Wallace Camargo, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim and Gregorio Valdez

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan express...

Authors: Addolorata Pisconti, Glen B. Banks, Farshad Babaeijandaghi, Nicole Dalla Betta, Fabio M. V. Rossi, Jeffrey S. Chamberlain and Bradley B. Olwin

Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease

Cellular models of muscle disease are taking on increasing importance with the large number of genes and mutations implicated in causing myopathies and the concomitant need to test personalized therapies. Deve...

Authors: Ellis Y. Kim, Patrick Page, Lisa M. Dellefave-Castillo, Elizabeth M. McNally and Eugene J. Wyatt

Six1 homeoprotein drives myofiber type IIA specialization in soleus muscle

Adult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription fac...

Authors: Iori Sakakibara, Maud Wurmser, Matthieu Dos Santos, Marc Santolini, Serge Ducommun, Romain Davaze, Anthony Guernec, Kei Sakamoto and Pascal Maire

Failed reinnervation in aging skeletal muscle

Skeletal muscle displays a marked accumulation of denervated myofibers at advanced age, which coincides with an acceleration of muscle atrophy.

Authors: Sudhakar Aare, Sally Spendiff, Madhusudanarao Vuda, Daren Elkrief, Anna Perez, Qinghua Wu, Dominique Mayaki, Sabah N. A. Hussain, Stefan Hettwer and Russell T. Hepple

p38α MAPK disables KMT1A-mediated repression of myogenic differentiation program

Master transcription factor MyoD can initiate the entire myogenic gene expression program which differentiates proliferating myoblasts into multinucleated myotubes. We previously demonstrated that histone meth...

Authors: Biswanath Chatterjee, David W. Wolff, Mathivanan Jothi, Munmun Mal and Asoke K. Mal

Embracing change: striated-for-smooth muscle replacement in esophagus development

The esophagus functions to transport food from the oropharyngeal region to the stomach via waves of peristalsis and transient relaxation of the lower esophageal sphincter. The gastrointestinal tract, including...

Authors: Robert S. Krauss, Daisuke Chihara and Anthony I. Romer

ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments

Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced ca...

Authors: Shinji Hatakeyama, Serge Summermatter, Marie Jourdain, Stefan Melly, Giulia C. Minetti and Estelle Lach-Trifilieff

Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle

The greater susceptibility to contraction-induced skeletal muscle injury (fragility) is an important dystrophic feature and tool for testing preclinic dystrophin-based therapies for Duchenne muscular dystrophy...

Authors: Pauline Roy, Fredérique Rau, Julien Ochala, Julien Messéant, Bodvael Fraysse, Jeanne Lainé, Onnik Agbulut, Gillian Butler-Browne, Denis Furling and Arnaud Ferry

Characterization of a Dmd ^EGFP reporter mouse as a tool to investigate dystrophin expression

Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as a structural link between the cytoskeleton and the extracellular matrix via the dystrophin-associated protein complex (DAPC...

Authors: Mina V. Petkova, Susanne Morales-Gonzales, Karima Relizani, Esther Gill, Franziska Seifert, Josefine Radke, Werner Stenzel, Luis Garcia, Helge Amthor and Markus Schuelke

Progressive impairment of Ca_V1.1 function in the skeletal muscle of mice expressing a mutant type 1 Cu/Zn superoxide dismutase (G93A) linked to amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3–5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events ...

Authors: Donald Beqollari, Christin F. Romberg, Gabriella Dobrowolny, Martina Martini, Andrew A. Voss, Antonio Musarò and Roger A. Bannister

Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice

Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a ...

Authors: Fabrizio Rinaldi, Yu Zhang, Ricardo Mondragon-Gonzalez, Jeffrey Harvey and Rita C. R. Perlingeiro

Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy

Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other ex...

Authors: Steven J. Foltz, Junna Luan, Jarrod A. Call, Ankit Patel, Kristen B. Peissig, Marisa J. Fortunato and Aaron M. Beedle

The lysine methyltransferase Ehmt2/G9a is dispensable for skeletal muscle development and regeneration

Euchromatic histone-lysine N-methyltransferase 2 (G9a/Ehmt2) is the main enzyme responsible for the apposition of H3K9 di-methylation on histones. Due to its dual role as an epigenetic regulator and in the regula...

Authors: Regan-Heng Zhang, Robert N. Judson, David Y. Liu, Jürgen Kast and Fabio M. V. Rossi

Erratum to: The beneficial role of proteolysis in skeletal muscle growth and stress adaptation

Authors: Ryan A. V. Bell, Mohammad Al-Khalaf and Lynn A. Megeney

Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction

Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle ...

Authors: Molly H. Jenkins, Sarah S. Alrowaished, Michelle F. Goody, Bryan D. Crawford and Clarissa A. Henry

The SH3 and cysteine-rich domain 3 (Stac3) gene is important to growth, fiber composition, and calcium release from the sarcoplasmic reticulum in postnatal skeletal muscle

The SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeleta...

Authors: Xiaofei Cong, Jonathan Doering, Davi A. G. Mazala, Eva R. Chin, Robert W. Grange and Honglin Jiang

Characterization of a multiprotein complex involved in excitation-transcription coupling of skeletal muscle

Electrical activity regulates the expression of skeletal muscle genes by a process known as “excitation-transcription” (E-T) coupling. We have demonstrated that release of adenosine 5′-triphosphate (ATP) durin...

Authors: Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich and Sonja Buvinic

The beneficial role of proteolysis in skeletal muscle growth and stress adaptation

Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature ...

Authors: Ryan A. V. Bell, Mohammad Al-Khalaf and Lynn A. Megeney

Dystrophin-deficient dogs with reduced myostatin have unequal muscle growth and greater joint contractures

Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a ...

Authors: Joe N. Kornegay, Daniel J. Bogan, Janet R. Bogan, Jennifer L. Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C. Warsing, Robert W. Grange, Mihye Ahn, Cynthia J. Balog-Alvarez, Steven W. Cotten, Monte S. Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra…

Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis

Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglyce...

Authors: Brianna D. Harfmann, Elizabeth A. Schroder, Maureen T. Kachman, Brian A. Hodge, Xiping Zhang and Karyn A. Esser

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

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