Articles

Complementary NAD⁺ replacement strategies fail to functionally protect dystrophin-deficient muscle

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder stemming from a loss of functional dystrophin. Current therapeutic options for DMD are limited, as small molecule modalities remain la...

Authors: David W. Frederick, Alan V. McDougal, Melisa Semenas, Johanna Vappiani, Andrea Nuzzo, John C. Ulrich, J. David Becherer, Frank Preugschat, Eugene L. Stewart, Daniel C. Sévin and H. Fritz Kramer

A novel chemical-combination screen in zebrafish identifies epigenetic small molecule candidates for the treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder and is one of the most common muscular dystrophies. There are currently few effective therapies to treat the disease, although many small-mo...

Authors: Gist H. Farr III, Melanie Morris, Arianna Gomez, Thao Pham, Elisabeth Kilroy, Elizabeth U. Parker, Shery Said, Clarissa Henry and Lisa Maves

Pro-myogenic small molecules revealed by a chemical screen on primary muscle stem cells

Satellite cells are the canonical muscle stem cells that regenerate damaged skeletal muscle. Loss of function of these cells has been linked to reduced muscle repair capacity and compromised muscle health in a...

Authors: Sean M. Buchanan, Feodor D. Price, Alessandra Castiglioni, Amanda Wagner Gee, Joel Schneider, Mark N. Matyas, Monica Hayhurst, Mohammadsharif Tabebordbar, Amy J. Wagers and Lee L. Rubin

Dnmt3b regulates DUX4 expression in a tissue-dependent manner in transgenic D4Z4 mice

Facioscapulohumeral muscular dystrophy (FSHD) is a skeletal muscle disorder that is caused by derepression of the transcription factor DUX4 in skeletal muscle cells. Apart from SMCHD1, DNMT3B was recently iden...

Authors: Linde F. Bouwman, Bianca den Hamer, Elwin P. Verveer, Lente J. S. Lerink, Yvonne D. Krom, Silvère M. van der Maarel and Jessica C. de Greef

High-throughput screening identifies modulators of sarcospan that stabilize muscle cells and exhibit activity in the mouse model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by mutations in the dystrophin gene. Loss of dystrophin prevents the formation of a critical connection between the muscle cell membran...

Authors: Cynthia Shu, Liubov Parfenova, Ekaterina Mokhonova, Judd R. Collado, Robert Damoiseaux, Jesus Campagna, Varghese John and Rachelle H. Crosbie

Exercise enhances mitochondrial fission and mitophagy to improve myopathy following critical limb ischemia in elderly mice via the PGC1a/FNDC5/irisin pathway

Elderly populations are susceptible to critical limb ischemia (CLI), but conventional treatments cannot significantly decrease amputation and mortality. Although exercise is an effective “non-pharmacological m...

Authors: Wuyang He, Peng Wang, Qingwei Chen and Chunqiu Li

Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism

Distal arthrogryposis (DA) is a group of autosomal dominant skeletal muscle diseases characterized by congenital contractures of distal limb joints. The most common cause of DA is a mutation of the embryonic m...

Authors: Yiming Guo, William A. Kronert, Karen H. Hsu, Alice Huang, Floyd Sarsoza, Kaylyn M. Bell, Jennifer A. Suggs, Douglas M. Swank and Sanford I. Bernstein

X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterisation

Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been describ...

Authors: Inès Barthélémy, Nadège Calmels, Robert B. Weiss, Laurent Tiret, Adeline Vulin, Nicolas Wein, Cécile Peccate, Carole Drougard, Christophe Beroud, Nathalie Deburgrave, Jean-Laurent Thibaud, Catherine Escriou, Isabel Punzón, Luis Garcia, Jean-Claude Kaplan, Kevin M. Flanigan…

The ties that bind: functional clusters in limb-girdle muscular dystrophy

The limb-girdle muscular dystrophies (LGMDs) are a genetically pleiomorphic class of inherited muscle diseases that are known to share phenotypic features. Selected LGMD genetic subtypes have been studied exte...

Authors: Elisabeth R. Barton, Christina A. Pacak, Whitney L. Stoppel and Peter B. Kang

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what ext...

Authors: Evi Masschelein, Gommaar D’Hulst, Joel Zvick, Laura Hinte, Inés Soro-Arnaiz, Tatiane Gorski, Ferdinand von Meyenn, Ori Bar-Nur and Katrien De Bock

Optimized method for extraction of exosomes from human primary muscle cells

Skeletal muscle is increasingly considered an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can affect physiological changes with an impact on different path...

Authors: Laura Le Gall, Zamalou Gisele Ouandaogo, Ekene Anakor, Owen Connolly, Gillian Butler Browne, Jeanne Laine, William Duddy and Stephanie Duguez

A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations

Single-cell RNA-sequencing (scRNA-seq) facilitates the unbiased reconstruction of multicellular tissue systems in health and disease. Here, we present a curated scRNA-seq dataset of human muscle samples from 1...

Authors: Andrea J. De Micheli, Jason A. Spector, Olivier Elemento and Benjamin D. Cosgrove

Human laminin-111 and laminin-211 protein therapy prevents muscle disease progression in an immunodeficient mouse model of LAMA2-CMD

Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating genetic disease caused by mutations in the LAMA2 gene. These mutations result in progressive muscle wasting and inflammation leadin...

Authors: Pamela Barraza-Flores, Hailey J. Hermann, Christina R. Bates, Tyler G. Allen, Timothy T. Grunert and Dean J. Burkin

Pluripotent stem cell-derived skeletal muscle fibers preferentially express myosin heavy-chain isoforms associated with slow and oxidative muscles

Skeletal muscle function is essential for health, and it depends on the proper activity of myofibers and their innervating motor neurons. Each adult muscle is composed of different types of myofibers with dist...

Authors: Tania Incitti, Alessandro Magli, Asher Jenkins, Karena Lin, Ami Yamamoto and Rita C. R. Perlingeiro

SMN-deficiency disrupts SERCA2 expression and intracellular Ca²⁺ signaling in cardiomyocytes from SMA mice and patient-derived iPSCs

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of alpha motor neurons and skeletal muscle atrophy. The disease is caused by mutations of the SMN1 gene that result in reduced fu...

Authors: Guzal Khayrullina, Kasey E. Moritz, James F. Schooley, Naheed Fatima, Coralie Viollet, Nikki M. McCormack, Jeremy T. Smyth, Martin L. Doughty, Clifton L. Dalgard, Thomas P. Flagg and Barrington G. Burnett

Exclusive vital labeling of myonuclei for studying myonuclear arrangement in mouse skeletal muscle tissue

The arrangement of myonuclei in skeletal muscle tissue has long been used as a biomarker for muscle health, but there is a dearth of in vivo exploration of potential effects of myonuclear organization on the f...

Authors: Robert Louis Hastings, Ryan T. Massopust, Seth G. Haddix, Young il Lee and Wesley J. Thompson

Functional effects of muscle PGC-1alpha in aged animals

PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of numerous metabolic processes. Exercise strongly induces PGC-1...

Authors: Steven Yang, Emanuele Loro, Shogo Wada, Boa Kim, Wei-Ju Tseng, Kristina Li, Tejvir S. Khurana and Zoltan Arany

Acute conversion of patient-derived Duchenne muscular dystrophy iPSC into myotubes reveals constitutive and inducible over-activation of TGFβ-dependent pro-fibrotic signaling

In Duchenne muscular dystrophy (DMD), DYSTROPHIN deficiency exposes myofibers to repeated cycles of contraction/degeneration, ultimately leading to muscle loss and replacement by fibrotic tissue. DMD pathology...

Authors: Luca Caputo, Alice Granados, Jessica Lenzi, Alessandro Rosa, Slimane Ait-Si-Ali, Pier Lorenzo Puri and Sonia Albini

Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model

Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key pr...

Authors: Thanh Nguyen, T. Scott Bowen, Antje Augstein, Antje Schauer, Alexander Gasch, Axel Linke, Siegfried Labeit and Volker Adams

Angiotensin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice

Transforming growth factor beta (TGF-β)-Smad2/3 is the major signaling pathway of fibrosis, which is characterized by the excessive production and accumulation of extracellular matrix (ECM) components, includi...

Authors: Naoya Kakutani, Shingo Takada, Hideo Nambu, Junichi Matsumoto, Takaaki Furihata, Takashi Yokota, Arata Fukushima and Shintaro Kinugawa

Efficient engraftment of pluripotent stem cell-derived myogenic progenitors in a novel immunodeficient mouse model of limb girdle muscular dystrophy 2I

Defects in α-dystroglycan (DG) glycosylation characterize a group of muscular dystrophies known as dystroglycanopathies. One of the key effectors in the α-DG glycosylation pathway is the glycosyltransferase fu...

Authors: Karim Azzag, Carolina Ortiz-Cordero, Nelio A. J. Oliveira, Alessandro Magli, Sridhar Selvaraj, Sudheer Tungtur, Weston Upchurch, Paul A. Iaizzo, Qi Long Lu and Rita C. R. Perlingeiro

Correction to: Expressing a Z-disk nebulin fragment innebulin-deficient mouse muscle: effects on muscle structure and function

Following the publication of this paper [1], it was brought to the authors’ attention that one of the contributing authors was left off of the paper. The authors apologize for the unfortunate oversight. In thi...

Authors: Frank Li, Justin Kolb, Julie Crudele, Paola Tonino, Zaynab Hourani, John E. Smith III, Jeffrey S. Chamberlain and Henk Granzier

Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity

All types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant activation of the somatically silent DUX4 gene, the expression of which initiates a cascade of cellular events ultimately lead...

Authors: Takako I. Jones, Guo-Liang Chew, Pamela Barraza-Flores, Spencer Schreier, Monique Ramirez, Ryan D. Wuebbles, Dean J. Burkin, Robert K. Bradley and Peter L. Jones

High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers

Skeletal muscles are composed of a heterogeneous collection of fiber types with different physiological adaption in response to a stimulus and disease-related conditions. Each fiber has a specific molecular ex...

Authors: Sebastian Kallabis, Lena Abraham, Stefan Müller, Verena Dzialas, Clara Türk, Janica Lea Wiederstein, Theresa Bock, Hendrik Nolte, Leonardo Nogara, Bert Blaauw, Thomas Braun and Marcus Krüger

A novel transplantable model of lung cancer-associated tissue loss and disrupted muscle regeneration

Cancer-associated muscle wasting (CAW), a symptom of cancer cachexia, is associated with approximately 20% of lung cancer deaths and remains poorly characterized on a mechanistic level. Current animal models f...

Authors: Paige C. Arneson-Wissink, Alexandra M. Ducharme and Jason D. Doles

Induction of the nicotinamide riboside kinase NAD⁺ salvage pathway in a model of sarcoplasmic reticulum dysfunction

Hexose-6-Phosphate Dehydrogenase (H6PD) is a generator of NADPH in the Endoplasmic/Sarcoplasmic Reticulum (ER/SR). Interaction of H6PD with 11β-hydroxysteroid dehydrogenase type 1 provides NADPH to support oxo...

Authors: Craig L. Doig, Agnieszka E. Zielinska, Rachel S. Fletcher, Lucy A. Oakey, Yasir S. Elhassan, Antje Garten, David Cartwright, Silke Heising, Ahmed Alsheri, David G. Watson, Cornelia Prehn, Jerzy Adamski, Daniel A. Tennant and Gareth G. Lavery

Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation

Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated cells (i.e., myofibers), and extracellul...

Authors: Jessy Etienne, Chao Liu, Colin M. Skinner, Michael J. Conboy and Irina M. Conboy

Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium modulators

Dystrophin deficiency sensitizes skeletal muscle of mice to eccentric contraction (ECC)-induced strength loss. ECC protocols distinguish dystrophin-deficient from healthy, wild type muscle, and test the effica...

Authors: Angus Lindsay, Cory W. Baumann, Robyn T. Rebbeck, Samantha L. Yuen, William M. Southern, James S. Hodges, Razvan L. Cornea, David D. Thomas, James M. Ervasti and Dawn A. Lowe

Expressing a Z-disk nebulin fragment in nebulin-deficient mouse muscle: effects on muscle structure and function

Nebulin is a critical thin filament-binding protein that spans from the Z-disk of the skeletal muscle sarcomere to near the pointed end of the thin filament. Its massive size and actin-binding property allows ...

Authors: Frank Li, Justin Kolb, Julie Crudele, Paola Tonino, Zaynab Hourani, John E. Smith III, Jeffrey S. Chamberlain and Henk Granzier

The ERG1a potassium channel increases basal intracellular calcium concentration and calpain activity in skeletal muscle cells

Skeletal muscle atrophy is the net loss of muscle mass that results from an imbalance in protein synthesis and protein degradation. It occurs in response to several stimuli including disease, injury, starvatio...

Authors: Clayton Whitmore, Evan P.S. Pratt, Luke Anderson, Kevin Bradley, Sawyer M. Latour, Mariam N. Hashmi, Albert K. Urazaev, Rod Weilbaecher, Judith K. Davie, Wen-Horng Wang, Gregory H. Hockerman and Amber L. Pond

Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by loss of sarcolemma connection to the extracellular matrix. Transgenic overexpression of the transmembrane protein sarcospan (SSPN) in the DMD mdx mouse model signifi...

Authors: Cynthia Shu, Ariana N. Kaxon-Rupp, Judd R. Collado, Robert Damoiseaux and Rachelle H. Crosbie

miR-1/206 downregulates splicing factor Srsf9 to promote C2C12 differentiation

Myogenesis is driven by specific changes in the transcriptome that occur during the different stages of muscle differentiation. In addition to controlled transcriptional transitions, several other post-transcr...

Authors: Kristen K. Bjorkman, Massimo Buvoli, Emily K. Pugach, Michael M. Polmear and Leslie A. Leinwand

mTORC2 affects the maintenance of the muscle stem cell pool

The mammalian target of rapamycin complex 2 (mTORC2), containing the essential protein rictor, regulates cellular metabolism and cytoskeletal organization by phosphorylating protein kinases, such as PKB/Akt, P...

Authors: Nathalie Rion, Perrine Castets, Shuo Lin, Leonie Enderle, Judith R. Reinhard and Markus A. Rüegg

In memoriam: Susan Abmayr (1956–2019) – “What do we do? Whatever it takes!”

Authors: Erika R. Geisbrecht and Mary K. Baylies

Two functional variants at 6p21.1 were associated with lean mass

Low lean body mass is the most important predictor of sarcopenia with strong genetic background. The aim of this study was to uncover genetic factors underlying lean mass development.

Authors: Yu-Fang Pei, Wen-Zhu Hu, Xiao-Lin Yang, Xin-Tong Wei, Gui-Juan Feng, Hong Zhang, Hui Shen, Qing Tian, Hong-Wen Deng and Lei Zhang

Barium chloride injures myofibers through calcium-induced proteolysis with fragmentation of motor nerves and microvessels

Local injection of BaCl₂ is an established model of acute injury to study the regeneration of skeletal muscle. However, the mechanism by which BaCl₂ causes muscle injury is unresolved. Because Ba²⁺ inhibits K⁺ ch...

Authors: Aaron B. Morton, Charles E. Norton, Nicole L. Jacobsen, Charmain A. Fernando, D. D. W. Cornelison and Steven S. Segal

LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force

Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can...

Authors: Duarte M. S. Ferreira, Arthur J. Cheng, Leandro Z. Agudelo, Igor Cervenka, Thomas Chaillou, Jorge C. Correia, Margareta Porsmyr-Palmertz, Manizheh Izadi, Alicia Hansson, Vicente Martínez-Redondo, Paula Valente-Silva, Amanda T. Pettersson-Klein, Jennifer L. Estall, Matthew M. Robinson, K. Sreekumaran Nair, Johanna T. Lanner…

Defective angiogenesis in CXCL12 mutant mice impairs skeletal muscle regeneration

During muscle regeneration, the chemokine CXCL12 (SDF-1) and the synthesis of some specific heparan sulfates (HS) have been shown to be critical. CXCL12 activity has been shown to be heavily influenced by its ...

Authors: David Hardy, Mylène Fefeu, Aurore Besnard, David Briand, Paméla Gasse, Fernando Arenzana-Seisdedos, Pierre Rocheteau and Fabrice Chrétien

Immunohistochemical phenotyping of T cells, granulocytes, and phagocytes in the muscle of cancer patients: association with radiologically defined muscle mass and gene expression

Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that in...

Authors: Ana Anoveros-Barrera, Amritpal S. Bhullar, Cynthia Stretch, Abha R. Dunichand-Hoedl, Karen J. B. Martins, Aja Rieger, David Bigam, Todd McMullen, Oliver F. Bathe, Charles T. Putman, Catherine J. Field, Vickie E. Baracos and Vera C. Mazurak

Ibuprofen inhibited migration of skeletal muscle cells in association with downregulation of p130cas and CrkII expressions

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat sports-related muscle injuries. However, NSAIDs were recently shown to impede the muscle healing process after acute injury. Migration o...

Authors: Chih-Hao Liao, Li-Ping Lin, Tung-Yang Yu, Chih-Chin Hsu, Jong-Hwei S. Pang and Wen-Chung Tsai

miR-146a deficiency does not aggravate muscular dystrophy in mdx mice

Duchenne muscular dystrophy (DMD) is a genetic disease evoked by a mutation in the dystrophin gene. It is associated with progressive muscle degeneration and increased inflammation. Up to this date, mainly ant...

Authors: Iwona Bronisz-Budzyńska, Katarzyna Chwalenia, Olga Mucha, Paulina Podkalicka, Karolina-Bukowska-Strakova, Alicja Józkowicz, Agnieszka Łoboda, Magdalena Kozakowska and Józef Dulak

NAD+ improves neuromuscular development in a zebrafish model of FKRP-associated dystroglycanopathy

Secondary dystroglycanopathies are muscular dystrophies that result from mutations in genes that participate in Dystroglycan glycosylation. Glycosylation of Dystroglycan is essential for muscle fibers to adher...

Authors: Erin C. Bailey, Sarah S. Alrowaished, Elisabeth A. Kilroy, Emma S. Crooks, Daisy M. Drinkert, Chaya M. Karunasiri, Joseph J. Belanger, Andre Khalil, Joshua B. Kelley and Clarissa A. Henry

Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells

Estrogen signaling is indispensable for muscle regeneration, yet the role of estrogen in the development of muscle inflammation, especially in the intramuscular T cell response, and the influence on the intrin...

Authors: Zhao Hong Liao, Tao Huang, Jiang Wei Xiao, Rui Cai Gu, Jun Ouyang, Gang Wu and Hua Liao

Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific

Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of tra...

Authors: Ryan G. Paul, Alex S. Hennebry, Marianne S. Elston, John V. Conaglen and Chris D. McMahon

Muscle injury-induced hypoxia alters the proliferation and differentiation potentials of muscle resident stromal cells

Trauma-induced heterotopic ossification (HO) is a complication that develops under three conditions: the presence of an osteogenic progenitor cell, an inducing factor, and a permissive environment. We previous...

Authors: Geneviève Drouin, Vanessa Couture, Marc-Antoine Lauzon, Frédéric Balg, Nathalie Faucheux and Guillaume Grenier

Culturing C2C12 myotubes on micromolded gelatin hydrogels accelerates myotube maturation

Skeletal muscle contributes to roughly 40% of lean body mass, and its loss contributes to morbidity and mortality in a variety of pathogenic conditions. Significant insights into muscle function have been made...

Authors: Lance T. Denes, Lance A. Riley, Joseph R. Mijares, Juan D. Arboleda, Kendra McKee, Karyn A. Esser and Eric T. Wang

A GDF11/myostatin inhibitor, GDF11 propeptide-Fc, increases skeletal muscle mass and improves muscle strength in dystrophic mdx mice

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily. The GDF11 propeptide, which is derived from the GDF11 precursor protein, blocks the activity of GDF11 and i...

Authors: Quan Jin, Chunping Qiao, Jianbin Li, Bin Xiao, Juan Li and Xiao Xiao

Automated image-analysis method for the quantification of fiber morphometry and fiber type population in human skeletal muscle

The quantitative analysis of muscle histomorphometry has been growing in importance in both research and clinical settings. Accurate and stringent assessment of myofibers’ changes in size and number, and alter...

Authors: Perla C. Reyes-Fernandez, Baptiste Periou, Xavier Decrouy, Fréderic Relaix and François Jérôme Authier

Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation

Myopalladin (MYPN) is a component of the sarcomere that tethers nebulin in skeletal muscle and nebulette in cardiac muscle to alpha-actinin at the Z lines. Autosomal dominant MYPN mutations cause hypertrophic, di...

Authors: Luciano Merlini, Patrizia Sabatelli, Manuela Antoniel, Valeria Carinci, Fabio Niro, Giuseppe Monetti, Annalaura Torella, Teresa Giugliano, Cesare Faldini and Vincenzo Nigro

Targeted ablation of the cellular inhibitor of apoptosis 1 (cIAP1) attenuates denervation-induced skeletal muscle atrophy

Skeletal muscle atrophy is a pathological condition that contributes to morbidity in a variety of conditions including denervation, cachexia, and aging. Muscle atrophy is characterized as decreased muscle fibe...

Authors: Neena Lala-Tabbert, Rim Lejmi-Mrad, Kristen Timusk, Marina Fukano, Janelle Holbrook, Martine St-Jean, Eric C. LaCasse and Robert G. Korneluk