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Cells Apr 2022MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are... (Review)
Review
MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are upregulated during myogenesis and influence stem cells to differentiate into myogenic lineage cells. In this review, we summarize MRFs, their regulatory factors, such as TLE3, NF-κB, and MRF target genes, including non-myogenic genes such as taste receptors. Understanding the function of MRFs and the physiology or pathology of satellite cells will contribute to the development of cell therapy and drug discovery for muscle-related diseases.
Topics: Muscle Development; Muscle, Skeletal; MyoD Protein; Myogenic Regulatory Factors; Stem Cells
PubMed: 35563799
DOI: 10.3390/cells11091493 -
International Journal of Molecular... Aug 2023Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle... (Review)
Review
Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle regeneration gives rise to myofibers that have myonuclei in a central position, which contrasts the normal, peripheral position of myonuclei. Myofibers with central myonuclei are called regenerating myofibers and are the hallmark feature of muscle regeneration. An important and underappreciated aspect of muscle regeneration is the maturation of regenerating myofibers into a normal sized myofiber with peripheral myonuclei. Strikingly, very little is known about processes that govern regenerating myofiber maturation after muscle injury. As knowledge of myofiber formation and maturation during embryonic, fetal, and postnatal development has served as a foundation for understanding muscle regeneration, this narrative review discusses similarities and differences in myofiber maturation during muscle development and regeneration. Specifically, we compare and contrast myonuclear positioning, myonuclear accretion, myofiber hypertrophy, and myofiber morphology during muscle development and regeneration. We also discuss regenerating myofibers in the context of different types of myofiber necrosis (complete and segmental) after muscle trauma and injurious contractions. The overall goal of the review is to provide a framework for identifying cellular and molecular processes of myofiber maturation that are unique to muscle regeneration.
Topics: Humans; Muscle, Skeletal; Exercise; Hypertrophy; Muscle Development; Necrosis
PubMed: 37628725
DOI: 10.3390/ijms241612545 -
Biomedicine & Pharmacotherapy =... Sep 2023Cordycepin (with a molecular formula of CHNO), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling...
Cordycepin (with a molecular formula of CHNO), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.
Topics: MAP Kinase Signaling System; Cell Differentiation; Deoxyadenosines; Muscle Development
PubMed: 37453196
DOI: 10.1016/j.biopha.2023.115163 -
Methods in Molecular Biology (Clifton,... 2023Skeletal muscle is a highly ordered tissue composed of a complex network of a diverse variety of cells. The dynamic spatial and temporal interaction between these cells...
Skeletal muscle is a highly ordered tissue composed of a complex network of a diverse variety of cells. The dynamic spatial and temporal interaction between these cells during homeostasis and during times of injury gives the skeletal muscle its regenerative capacity. In order to properly understand the process of regeneration, a three-dimensional (3-D) imaging process must be conducted. While there have been several protocols studying 3-D imaging, it has primarily been focused on the nervous system. This protocol aims to outline the workflow for rendering a 3-D image of the skeletal muscle using spatial data from confocal microscope images. This protocol uses the ImageJ, Ilastik, and Imaris software for 3-D rendering and computational image analysis as both are relatively easy to use and have powerful segmentation capabilities.
Topics: Imaging, Three-Dimensional; Satellite Cells, Skeletal Muscle; Muscle, Skeletal; Image Processing, Computer-Assisted; Muscle Development; Cell Differentiation
PubMed: 36995614
DOI: 10.1007/978-1-0716-3036-5_32 -
Current Topics in Developmental Biology 2018The neuromuscular junction (NMJ) is the specialized site that connects the terminal of a motor neuron axon to skeletal muscle. As a synapse NMJ integrity is essential... (Review)
Review
The neuromuscular junction (NMJ) is the specialized site that connects the terminal of a motor neuron axon to skeletal muscle. As a synapse NMJ integrity is essential for transducing motor neuron signals that initiate skeletal muscle contraction. Many diseases and skeletal muscle aging are linked to impaired NMJ function and the associated muscle wasting. In this chapter we review the components of an NMJ and, the processes of NMJ development, maturation, and regeneration. Also, we briefly discuss the cellular and molecular mechanisms of NMJ decline in the context of disease and aging.
Topics: Animals; Humans; Models, Biological; Muscle Contraction; Muscle Development; Muscle, Skeletal; Muscular Diseases; Neuromuscular Junction; Regeneration; Synapses
PubMed: 29305005
DOI: 10.1016/bs.ctdb.2017.08.005 -
Acta Physiologica (Oxford, England) Feb 2020The multistep biological process of myogenesis is regulated by a variety of myoblast regulators, such as myogenic differentiation antigen, myogenin, myogenic regulatory... (Review)
Review
The multistep biological process of myogenesis is regulated by a variety of myoblast regulators, such as myogenic differentiation antigen, myogenin, myogenic regulatory factor, myocyte enhancer factor2A-D and myosin heavy chain. Proliferation and differentiation during skeletal muscle myogenesis contribute to the physiological function of muscles. Certain non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are involved in the regulation of muscle development, and the aberrant expressions of lncRNAs and circRNAs are associated with muscular diseases. In this review, we summarize the recent advances concerning the roles of lncRNAs and circRNAs in regulating the developmental aspects of myogenesis. These findings have remarkably broadened our understanding of the gene regulation mechanisms governing muscle proliferation and differentiation, which makes it more feasible to design novel preventive, diagnostic and therapeutic strategies for muscle disorders.
Topics: Animals; Cell Differentiation; Gene Expression Regulation; Humans; Muscle Development; Muscle, Skeletal; Muscular Diseases; RNA, Circular; RNA, Long Noncoding
PubMed: 31365949
DOI: 10.1111/apha.13356 -
Skeletal Muscle May 2023Skeletal muscle development and regeneration depend on cellular fusion of myogenic progenitors to generate multinucleated myofibers. These progenitors utilize two...
BACKGROUND
Skeletal muscle development and regeneration depend on cellular fusion of myogenic progenitors to generate multinucleated myofibers. These progenitors utilize two muscle-specific fusogens, Myomaker and Myomerger, which function by remodeling cell membranes to fuse to each other or to existing myofibers. Myomaker and Myomerger expression is restricted to differentiating progenitor cells as they are not detected in adult myofibers. However, Myomaker remains expressed in myofibers from mice with muscular dystrophy. Ablation of Myomaker from dystrophic myofibers results in reduced membrane damage, leading to a model where persistent fusogen expression in myofibers, in contrast to myoblasts, is harmful.
METHODS
Dox-inducible transgenic mice were developed to ectopically express Myomaker or Myomerger in the myofiber compartment of skeletal muscle. We quantified indices of myofiber membrane damage, such as serum creatine kinase and IgM myofibers, and assessed general muscle histology, including central nucleation, myofiber size, and fibrosis.
RESULTS
Myomaker or Myomerger expression in myofibers independently caused membrane damage at acute time points. This damage led to muscle pathology, manifesting with centrally nucleated myofibers and muscle atrophy. Dual expression of both Myomaker and Myomerger in myofibers exacerbated several aspects of muscle pathology compared to expression of either fusogen by itself.
CONCLUSIONS
These data reveal that while myofibers can tolerate some level of Myomaker and Myomerger, expression of a single fusogen above a threshold or co-expression of both fusogens is damaging to myofibers. These results explain the paradigm that their expression in myofibers can have deleterious consequences in muscle pathologies and highlight the need for their highly restricted expression during myogenesis and fusion.
Topics: Mice; Animals; Membrane Proteins; Muscle Proteins; Muscle, Skeletal; Myoblasts; Mice, Transgenic; Muscle Development
PubMed: 37127758
DOI: 10.1186/s13395-023-00317-z -
Seminars in Cell & Developmental Biology Aug 2015Like other subclasses within the PAX transcription factor family, PAX3 and PAX7 play important roles in the emergence of a number of different tissues during... (Review)
Review
Like other subclasses within the PAX transcription factor family, PAX3 and PAX7 play important roles in the emergence of a number of different tissues during development. PAX3 regulates neural crest and, together with its orthologue PAX7, is also expressed in parts of the central nervous system. In this chapter we will focus on their role in skeletal muscle. Both factors are key regulators of myogenesis where Pax3 plays a major role during early skeletal muscle formation in the embryo while Pax7 predominates during post-natal growth and muscle regeneration in the adult. We review the expression and functions of these factors in the myogenic context. We also discuss mechanistic aspects of PAX3/7 function and modulation of their activity by interaction with other proteins, as well as the post-transcriptional and transcriptional regulation of their expression.
Topics: Animals; Cell Differentiation; Cell Proliferation; Humans; Muscle Development; PAX3 Transcription Factor; PAX7 Transcription Factor; Paired Box Transcription Factors
PubMed: 26424495
DOI: 10.1016/j.semcdb.2015.09.017 -
Vitamins and Hormones 2021Regeneration of skeletal muscle is a finely tuned process which is depending on muscle stem cells, a population of stem cells in skeletal muscle which is also termed...
Regeneration of skeletal muscle is a finely tuned process which is depending on muscle stem cells, a population of stem cells in skeletal muscle which is also termed satellite cells. Muscle stem cells are a prerequisite for regeneration of skeletal muscle. Of note, the muscle stem cell population is heterogeneous and subpopulations can be identified depending on gene expression or phenotypic traits. However, all muscle stem cells express the transcription factor Pax7 and their functionality is tightly controlled by intrinsic signaling pathways and extrinsic signals. The latter ones include signals form the stem cell niche as well as circulating factors such as growth factors and hormones. Among them are Wnt proteins, growth factors like IGF-1 or FGF-2 and hormones such as thyroid hormones and the anti-aging hormone Klotho. A highly orchestrated interplay between those factors and muscle stem cells is important for their full functionality and ultimately regeneration of skeletal muscle as outlined here.
Topics: Cell Differentiation; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Stem Cells
PubMed: 33752822
DOI: 10.1016/bs.vh.2021.02.012 -
Bioscience Reports Jan 2023Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells (MuSCs). Molecular and cellular components of... (Review)
Review
Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells (MuSCs). Molecular and cellular components of the MuSC niche, such as immune cells, play key roles to coordinate MuSC function and to orchestrate muscle regeneration. An abnormal infiltration of immune cells and/or imbalance of pro- and anti-inflammatory cytokines could lead to MuSC dysfunctions that could have long lasting effects on muscle function. Different genetic variants were shown to cause muscular dystrophies that intrinsically compromise MuSC function and/or disturb their microenvironment leading to impaired muscle regeneration that contributes to disease progression. Alternatively, many acquired myopathies caused by comorbidities (e.g., cardiopulmonary or kidney diseases), chronic inflammation/infection, or side effects of different drugs can also perturb MuSC function and their microenvironment. The goal of this review is to comprehensively summarize the current knowledge on acquired myopathies and their impact on MuSC function. We further describe potential therapeutic strategies to restore MuSC regenerative capacity.
Topics: Humans; Muscular Diseases; Muscle, Skeletal; Myoblasts; Muscle Development; Inflammation
PubMed: 36538023
DOI: 10.1042/BSR20220284