-
Wiley Interdisciplinary Reviews.... Jan 2020Decades of research in skeletal muscle physiology have provided multiscale insights into the structural and functional complexity of this important anatomical tissue,... (Review)
Review
Decades of research in skeletal muscle physiology have provided multiscale insights into the structural and functional complexity of this important anatomical tissue, designed to accomplish the task of generating contraction, force and movement. Skeletal muscle can be viewed as a biomechanical device with various interacting components including the autonomic nerves for impulse transmission, vasculature for efficient oxygenation, and embedded regulatory and metabolic machinery for maintaining cellular homeostasis. The "omics" revolution has propelled a new era in muscle research, allowing us to discern minute details of molecular cross-talk required for effective coordination between the myriad interacting components for efficient muscle function. The objective of this review is to provide a systems-level, comprehensive mapping the molecular mechanisms underlying skeletal muscle structure and function, in health and disease. We begin this review with a focus on molecular mechanisms underlying muscle tissue development (myogenesis), with an emphasis on satellite cells and muscle regeneration. We next review the molecular structure and mechanisms underlying the many structural components of the muscle: neuromuscular junction, sarcomere, cytoskeleton, extracellular matrix, and vasculature surrounding muscle. We highlight aberrant molecular mechanisms and their possible clinical or pathophysiological relevance. We particularly emphasize the impact of environmental stressors (inflammation and oxidative stress) in contributing to muscle pathophysiology including atrophy, hypertrophy, and fibrosis. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Developmental Biology > Developmental Processes in Health and Disease Models of Systems Properties and Processes > Cellular Models.
Topics: Animals; Biophysical Phenomena; Extracellular Matrix; Humans; Models, Biological; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Neuromuscular Junction; Satellite Cells, Skeletal Muscle; Synapses
PubMed: 31407867
DOI: 10.1002/wsbm.1462 -
Journal of Sport Rehabilitation Apr 2017Eccentric-contraction-induced skeletal muscle injuries, included in what is clinically referred to as muscle strains, are among the most common injuries treated in the... (Review)
Review
Eccentric-contraction-induced skeletal muscle injuries, included in what is clinically referred to as muscle strains, are among the most common injuries treated in the sports medicine setting. Although patients with mild injuries often fully recover to their preinjury levels, patients who suffer moderate or severe injuries can have a persistent weakness and loss of function that is refractory to rehabilitation exercises and currently available therapeutic interventions. The objectives of this review were to describe the fundamental biophysics of force transmission in muscle and the mechanism of muscle-strain injuries, as well as the cellular and molecular processes that underlie the repair and regeneration of injured muscle tissue. The review also summarizes how commonly used therapeutic modalities affect muscle regeneration and opportunities to further improve our treatment of skeletal muscle strain injuries.
Topics: Humans; Muscle, Skeletal; Muscular Atrophy; Recovery of Function; Regeneration; Sprains and Strains
PubMed: 27992284
DOI: 10.1123/jsr.2016-0107 -
Small (Weinheim An Der Bergstrasse,... Jun 2019Skeletal muscle tissue engineering (SMTE) aims at repairing defective skeletal muscles. Until now, numerous developments are made in SMTE; however, it is still... (Review)
Review
Skeletal muscle tissue engineering (SMTE) aims at repairing defective skeletal muscles. Until now, numerous developments are made in SMTE; however, it is still challenging to recapitulate the complexity of muscles with current methods of fabrication. Here, after a brief description of the anatomy of skeletal muscle and a short state-of-the-art on developments made in SMTE with "conventional methods," the use of 3D bioprinting as a new tool for SMTE is in focus. The current bioprinting methods are discussed, and an overview of the bioink formulations and properties used in 3D bioprinting is provided. Finally, different advances made in SMTE by 3D bioprinting are highlighted, and future needs and a short perspective are provided.
Topics: Bioprinting; Cell Culture Techniques; Cells, Cultured; Humans; Muscle, Skeletal; Printing, Three-Dimensional; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds
PubMed: 31012262
DOI: 10.1002/smll.201805530 -
Mechanisms of Ageing and Development Dec 2021Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive... (Review)
Review
Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive phenotype, characterized by profound chromatin alterations and a robust senescence-associated secretory phenotype (SASP) that exerts negative effects on tissue health, both locally and systemically. In preclinical models, pharmacological agents that eliminate senescent cells (senotherapeutics) restore health and youthful properties in multiple tissues. To date, however, very little is understood about the vulnerability of terminally-differentiated skeletal muscle fibers and the resident mononuclear cells that populate the interstitial microenvironment of skeletal muscle to senescence, and their contribution to the onset and progression of skeletal muscle loss and dysfunction with aging. Scientific advances in these areas have the potential to highlight new therapeutic approaches to optimize late-life muscle health. To this end, this review highlights the current evidence and the key questions that need to be addressed to advance the field's understanding of cellular senescence as a mediator of skeletal muscle aging and the potential for emerging senescent cell-targeting therapies to counter age-related deficits in muscle mass, strength, and function. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.
Topics: Cellular Senescence; Humans; Muscle, Skeletal; Sarcopenia; Senescence-Associated Secretory Phenotype; Senotherapeutics
PubMed: 34742751
DOI: 10.1016/j.mad.2021.111595 -
Open Biology Dec 2021Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of... (Review)
Review
Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.
Topics: Adipogenesis; Animals; Cell Differentiation; Gene Regulatory Networks; Homeostasis; Humans; Mesenchymal Stem Cells; Muscle, Skeletal; Regeneration; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 34875199
DOI: 10.1098/rsob.210110 -
Journal of Cachexia, Sarcopenia and... Dec 2022Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation...
BACKGROUND
Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation of skeletal muscle cells and their utility in skeletal muscle tissue engineering with the aim to model skeletal muscle regeneration and dystrophy in vitro.
METHODS
Key steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors followed by primary and secondary foetal myogenesis into three-dimensional muscle. To simulate Duchenne muscular dystrophy (DMD), a patient-specific induced pluripotent stem cell line was compared to a CRISPR/Cas9-edited isogenic control line.
RESULTS
The established skeletal muscle differentiation protocol robustly and faithfully recapitulates critical steps of embryonic myogenesis in two-dimensional and three-dimensional cultures, resulting in functional human skeletal muscle organoids (SMOs) and engineered skeletal muscles (ESMs) with a regeneration-competent satellite-like cell pool. Tissue-engineered muscle exhibits organotypic maturation and function (up to 5.7 ± 0.5 mN tetanic twitch tension at 100 Hz in ESM). Contractile performance could be further enhanced by timed thyroid hormone treatment, increasing the speed of contraction (time to peak contraction) as well as relaxation (time to 50% relaxation) of single twitches from 107 ± 2 to 75 ± 4 ms (P < 0.05) and from 146 ± 6 to 100 ± 6 ms (P < 0.05), respectively. Satellite-like cells could be documented as largely quiescent PAX7 cells (75 ± 6% Ki67 ) located adjacent to muscle fibres confined under a laminin-containing basal membrane. Activation of the engineered satellite-like cell niche was documented in a cardiotoxin injury model with marked recovery of contractility to 57 ± 8% of the pre-injury force 21 days post-injury (P < 0.05 compared to Day 2 post-injury), which was completely blocked by preceding irradiation. Absence of dystrophin in DMD ESM caused a marked reduction of contractile force (-35 ± 7%, P < 0.05) and impaired expression of fast myosin isoforms resulting in prolonged contraction (175 ± 14 ms, P < 0.05 vs. gene-edited control) and relaxation (238 ± 22 ms, P < 0.05 vs. gene-edited control) times. Restoration of dystrophin levels by gene editing rescued the DMD phenotype in ESM.
CONCLUSIONS
We introduce human muscle models with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease and repair.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Muscle Development; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal
PubMed: 36254806
DOI: 10.1002/jcsm.13094 -
Nutrients Aug 2019The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal... (Review)
Review
The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal cells, including skeletal muscles. Vitamin D deficiency may cause deficits in strength, and lead to fatty degeneration of type II muscle fibers, which has been found to negatively correlate with physical performance. Vitamin D supplementation has been shown to improve vitamin D status and can positively affect skeletal muscles. The purpose of this study is to summarize the current evidence of the relationship between vitamin D, skeletal muscle function and physical performance in athletes. Additionally, we will discuss the effect of vitamin D supplementation on athletic performance in players. Further studies are necessary to fully characterize the underlying mechanisms of calcitriol action in the human skeletal muscle tissue, and to understand how these actions impact the athletic performance in athletes.
Topics: Animals; Athletes; Athletic Performance; Calcitriol; Dietary Supplements; Humans; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Nutritional Status; Receptors, Calcitriol; Signal Transduction; Vitamin D Deficiency
PubMed: 31382666
DOI: 10.3390/nu11081800 -
The FEBS Journal Oct 2018Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC... (Review)
Review
Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC antibodies has provided a powerful tool to define the fiber types present in skeletal muscles, their functional properties, their response to conditions that affect muscle plasticity and their changes in muscle disorders. Cardiomyocyte heterogeneity has been revealed by the serendipitous observation that different MyHCs are present in atrial and ventricular myocardium and in heart conduction tissue. Developmental MyHCs present in embryonic and fetal/neonatal skeletal muscle are re-expressed during muscle regeneration and can be used to identify regenerating fibers in muscle diseases. MyHC isoforms provide cell type-specific markers to identify the signaling pathways that control muscle cell identity and are an essential reference to interpret the results of single-cell transcriptomics and proteomics.
Topics: Animals; Antibodies, Monoclonal; Gene Expression Regulation, Developmental; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosin Heavy Chains; Protein Isoforms
PubMed: 29761627
DOI: 10.1111/febs.14502 -
Nature Reviews. Immunology Mar 2017Diseases of muscle that are caused by pathological interactions between muscle and the immune system are devastating, but rare. However, muscle injuries that involve... (Review)
Review
Diseases of muscle that are caused by pathological interactions between muscle and the immune system are devastating, but rare. However, muscle injuries that involve trauma and regeneration are fairly common, and inflammation is a clear feature of the regenerative process. Investigations of the inflammatory response to muscle injury have now revealed that the apparently nonspecific inflammatory response to trauma is actually a complex and coordinated interaction between muscle and the immune system that determines the success or failure of tissue regeneration.
Topics: Animals; Humans; Muscle, Skeletal; Regeneration
PubMed: 28163303
DOI: 10.1038/nri.2016.150 -
Biomedicine & Pharmacotherapy =... Jun 2023Skeletal muscle is the most extensive tissue in mammals, and they perform several functions; it is derived from paraxial mesodermal somites and undergoes hyperplasia and... (Review)
Review
Skeletal muscle is the most extensive tissue in mammals, and they perform several functions; it is derived from paraxial mesodermal somites and undergoes hyperplasia and hypertrophy to form multinucleated, contractile, and functional muscle fibers. Skeletal muscle is a complex heterogeneous tissue composed of various cell types that establish communication strategies to exchange biological information; therefore, characterizing the cellular heterogeneity and transcriptional signatures of skeletal muscle is central to understanding its ontogeny's details. Studies of skeletal myogenesis have focused primarily on myogenic cells' proliferation, differentiation, migration, and fusion and ignored the intricate network of cells with specific biological functions. The rapid development of single-cell sequencing technology has recently enabled the exploration of skeletal muscle cell types and molecular events during development. This review summarizes the progress in single-cell RNA sequencing and its applications in skeletal myogenesis, which will provide insights into skeletal muscle pathophysiology.
Topics: Animals; Muscle, Skeletal; Muscle Fibers, Skeletal; Cell Differentiation; Mammals; Muscle Development; Developmental Biology; Sequence Analysis, RNA
PubMed: 37003036
DOI: 10.1016/j.biopha.2023.114631