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Dilyana Filipova, Margit Henry, Tamara Rotshteyn, Anna Brunn, Mariana Carstov, Martina Deckert, Jürgen Hescheler, Agapios Sachinidis, Gabriele Pfitzer, Symeon Papadopoulos
In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels-the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)-underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14...
2018: PloS One
Gary Hin-Fai Yam, Ericia Pei-Wen Teo, Melina Setiawan, Matthew J Lovatt, Nur Zahirah Binte M Yusoff, Matthias Fuest, Bee-Tin Goh, Jodhbir S Mehta
Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest...
March 13, 2018: Journal of Cellular and Molecular Medicine
Deana Haralampieva, Souzan Salemi, Thomas Betzel, Ivana Dinulovic, Stefanie D Krämer, Roger Schibli, Tullio Sulser, Christoph Handschin, Simon M Ametamey, Daniel Eberli
While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1 α ), key regulator of exercise-mediated adaptation...
2018: Stem Cells International
David Castel, Meryem B Baghdadi, Sébastien Mella, Barbara Gayraud-Morel, Virginie Marty, Jérôme Cavaillé, Christophe Antoniewski, Shahragim Tajbakhsh
Skeletal muscle satellite cells are quiescent adult resident stem cells that activate, proliferate and differentiate to generate myofibres following injury. They harbour a robust proliferation potential and self-renewing capacity enabling lifelong muscle regeneration. Although several classes of microRNAs were shown to regulate adult myogenesis, systematic examination of stage-specific microRNAs during lineage progression from the quiescent state is lacking. Here we provide a genome-wide assessment of the expression of small RNAs during the quiescence/activation transition and differentiation by RNA-sequencing...
March 9, 2018: Scientific Reports
Claudia Miersch, Katja Stange, Monika Röntgen
BACKGROUND: Satellite cells (SC) and their descendants, muscle precursor cells (MPC), play a key role in postnatal muscle development, regeneration, and plasticity. Several studies have provided evidence that SC and MPC represent a heterogeneous population differing in their biochemical and functional properties. The identification and characterization of functionally divergent SC subpopulations should help to reveal the precise involvement of SC/MPC in these myogenic processes. The aim of the present work was therefore to separate SC subpopulations by using Percoll gradients and to characterize their myogenic marker profiles and their functional properties (adhesion, proliferation, and differentiation)...
March 9, 2018: BMC Cell Biology
F Chen, W Yuan, X Mo, J Zhuang, Y Wang, J Chen, Z Jiang, X Zhu, Q Zeng, Y Wan, F Li, Y Shi, L Cao, X Fan, S Luo, X Ye, Y Chen, G Dai, J Gao, X Wang, H Xie, P Zhu, Y Li, X Wu
Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. Zebrafish Fhl1A is the homologue of human FHL1. In the present study, we showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK...
March 7, 2018: Current Molecular Medicine
Carolyn M Dancevic, Yann Gibert, Joachim Berger, Adam D Smith, Clifford Liongue, Nicole Stupka, Alister C Ward, Daniel R McCulloch
The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5...
March 7, 2018: International Journal of Molecular Sciences
Alexis H Bennett, Marie-Francoise O'Donohue, Stacey R Gundry, Aye T Chan, Jeffrey Widrick, Isabelle Draper, Anirban Chakraborty, Yi Zhou, Leonard I Zon, Pierre-Emmanuel Gleizes, Alan H Beggs, Vandana A Gupta
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration...
March 2018: PLoS Genetics
Xian-Tao Zeng, Xiao-Ping Liu, Tong-Zu Liu, Xing-Huan Wang
The present study was aimed to investigate the relationship between the expression of collagen type V alpha 2 chain (COL5A2) and clinical outcomes of patients with bladder cancer.Chi-square test and log-rank-based survival analysis were performed to assess the correlation of COL5A2 expression with clinical characteristics and survivals of patients with bladder cancer using GSE13507. Gene set enrichment analysis was conducted to study the relevant mechanisms.Bladder cancer patients in COL5A2 low expression group were associated with better invasiveness (P < ...
March 2018: Medicine (Baltimore)
Chayanit Chaweewannakorn, Masahiro Tsuchiya, Masashi Koide, Hiroyasu Hatakeyama, Yukinori Tanaka, Shinichirou Yoshida, Shunji Sugawara, Yoshihiro Hagiwara, Keiichi Sasaki, Makoto Kanzaki
Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double-knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of pro-inflammatory factors including IL-6 and delayed increase of PAX7-positive satellite cells post-injury as compared with those of wild-type (WT) mice...
March 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yu-Taro Noguchi, So-Ichiro Fukada
Skeletal muscle composes 30-40% of our body weight and is formed by multinuclear cells called myofibers. The formation of myofiber depends on the dynamic proliferation, differentiation and fusion of the myogenic progenitors during development. In the adult stage, the skeletal muscle exhibits excellent regeneration ability as well, depended on the muscle stem(satellite)cells that generate and repair myofibers. In this review, we would like to introduce ① the mechanisms of myogenic progenitor-dependent myofiber formation in myogenesis, ② the common fusion mechanism for myogenesis and muscle regeneration, and ③ the current status and prospects for clinical application utilizing satellite cells...
2018: Clinical Calcium
Zong-Kang Zhang, Jie Li, Daogang Guan, Chao Liang, Zhenjian Zhuo, Jin Liu, Aiping Lu, Ge Zhang, Bao-Ting Zhang
BACKGROUND: Skeletal muscle atrophy induced by either aging (sarcopenia) or mechanical unloading is associated with serious health consequences. Long non-coding RNAs (lncRNAs) are implicated as important regulators in numerous physiological and pathological processes. METHODS: Microarray analysis was performed to identify the differentially expressed lncRNAs in skeletal muscle between adult and aged mice. The most decreased lncRNA in aged skeletal muscle was identified...
March 7, 2018: Journal of Cachexia, Sarcopenia and Muscle
Mailin Gan, Jingjing Du, Linyuan Shen, Dongli Yang, Anan Jiang, Qiang Li, Yanzhi Jiang, Guoqing Tang, Mingzhou Li, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
The development of skeletal muscle is a complex process involving the proliferation, differentiation, apoptosis, and changing of muscle fiber types in myoblasts. Many reports have described the involvement of microRNAs in the myogenesis of myoblasts. In this study, we found that the expression of miR-152 was gradually down-regulated during myoblast proliferation, but gradually up-regulated during the differentiation of myoblasts. Transfection with miR-152 mimics restrained cell proliferation and decreased the expression levels of cyclin E, CDK4, and cyclin D1, but promoted myotube formation and significantly increased the mRNA expression levels of MyHC, MyoD, MRF4, and MyoG in C2C12 myoblasts...
March 5, 2018: In Vitro Cellular & Developmental Biology. Animal
Xiao Cheng, Jingjing Du, Linyuan Shen, Zhendong Tan, Dongmei Jiang, Anan Jiang, Qiang Li, Guoqing Tang, Yanzhi Jiang, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
Myogenic differentiation, which occurs in the process of muscle development, is a highly ordered process. Increasing evidence indicates that microRNAs (miRNAs) are important regulators in myogenic processes. In this study, we found that miR-204-5p expression gradually decreased when myoblasts were induced to differentiate. Our results suggested that miR-204-5p blunted myoblast differentiation, which was accompanied with a decreased proportion of myosin heavy chain (MyHC)-positive cells in myoblasts with augmented expression of miR-204-5p...
March 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Joanne Young, Yoran Margaron, Mathieu Fernandes, Eve Duchemin-Pelletier, Joris Michaud, Mélanie Flaender, Oana Lorintiu, Sébastien Degot, Pauline Poydenot
Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays...
March 1, 2018: SLAS Discovery
Can Zhou, Li Rao, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are multi-isomeric scaffolding proteins. Nesprin-1 and -2 are highly expressed in skeletal and cardiac muscles and together with SUN (Sad1p/UNC84) domain-containing proteins form the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex at the nuclear envelope in association with lamin A/C and emerin. Mutations in nesprin-1/2 have been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM)...
February 27, 2018: Biochemical Society Transactions
Wanling Xuan, Yan Wang, Yaoliang Tang, Ailia Ali, Hong Hu, Mark Maienschein-Cline, Muhammad Ashraf
Cardiac progenitor cells (CPCs) being multipotent offer a promising source for cardiac repair due to their ability to proliferate and multiply into cardiac lineage cells. Here, we explored a novel strategy for human CPCs generation from human induced pluripotent stem cells (hiPSCs) using a cardiogenic small molecule, isoxazole (ISX-9) and their ability to grow in the scar tissue for functional improvement in the infarcted myocardium. CPCs were induced from hiPSCs with ISX-9. CPCs were characterized by immunocytochemistry and RT-PCR...
February 26, 2018: Shock
Osvaldo Contreras, Maximiliano Villarreal, Enrique Brandan
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are effective therapies with demonstrated antineoplastic activity. Nilotinib is a second-generation FDA-approved TKI designed to overcome Imatinib resistance and intolerance in patients with chronic myelogenous leukemia (CML). Interestingly, TKIs have also been shown to be an efficient treatment for several non-malignant disorders such fibrotic diseases, including those affecting skeletal muscles. METHODS: We investigated the role of Nilotinib on skeletal myogenesis using the well-established C2C12 myoblast cell line...
February 20, 2018: Skeletal Muscle
Shu-Juan Xie, Jun-Hao Li, Hua-Feng Chen, Ye-Ya Tan, Shu-Rong Liu, Yin Zhang, Hui Xu, Jian-Hua Yang, Shun Liu, Ling-Ling Zheng, Mian-Bo Huang, Yan-Hua Guo, Qi Zhang, Hui Zhou, Liang-Hu Qu
Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted...
February 15, 2018: Cell Death and Differentiation
Mitsushiro Nakatomi, Angela Quispe-Salcedo, Masaka Sakaguchi, Hiroko Ida-Yonemochi, Hideyuki Okano, Hayato Ohshima
The Nestin gene encodes type VI intermediate filament and is known to be expressed in undifferentiated cells during neurogenesis and myogenesis. To regulate Nestin expression, the first or second intron enhancer is activated in a tissue-dependent manner, for example, the former in mesodermal cells and the latter in neural stem cells. Although Nestin has also been used as a differentiation marker for odontoblasts during tooth development, how Nestin expression is regulated in odontoblasts remains unclear. Therefore, this study aimed to compare the expression patterns of Nestin-GFP (green fluorescent protein) with that of endogenous Nestin in developing teeth of Nestin-EGFP (enhanced GFP) transgenic mice, in which the second intron enhancer is connected with the EGFP domain, at postnatal 7d, 3w, and 8w...
February 14, 2018: Histochemistry and Cell Biology
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