The quasi-parallel lives of satellite cells and atrophying muscle

Biressi, Stefano; Gopinath, Suchitra D.

doi:10.3389/fnagi.2015.00140

Cited by 5 publications

(6 citation statements)

References 223 publications

(283 reference statements)

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“…Several recent reports have addressed the molecular changes taking place in the stem cell compartment accompanying various forms of atrophy [57]. Studies examining the changes in SC compartment in muscle wasting conditions such as aging and hind limb suspension have reported variable results from a reduction to no differences in SC numbers under these conditions [58–60].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor

Gopinath

2017

Skeletal Muscle

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BackgroundAlthough skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D signaling are less clear. To determine the molecular consequences of vitamin D signaling, we analyzed the role of signal transducer and activator of transcription 3 (Stat3) signaling, a known contributor to various muscle wasting pathologies, in skeletal muscles.MethodsWe isolated soleus (slow) and tibialis anterior (fast) muscles from mice lacking the vitamin D receptor (VDR−/−) and used western blot analysis, quantitative RTPCR, and pharmacological intervention to analyze muscle atrophy in VDR−/− mice.ResultsWe found that slow and fast subsets of muscles of the VDR−/− mice displayed elevated levels of phosphorylated Stat3 accompanied by an increase in Myostatin expression and signaling. Consequently, we observed reduced activity of mammalian target of rapamycin (mTOR) signaling components, ribosomal S6 kinase (p70S6K) and ribosomal S6 protein (rpS6), that regulate protein synthesis and cell size, respectively. Concomitantly, we observed an increase in atrophy regulators and a block in autophagic gene expression. An examination of the upstream regulation of Stat3 levels in VDR−/− muscles revealed an increase in IL-6 protein expression in the soleus, but not in the tibialis anterior muscles. To investigate the involvement of satellite cells (SCs) in atrophy in VDR−/− mice, we found that there was no significant deficit in SC numbers in VDR−/− muscles compared to the wild type. Unlike its expression within VDR−/− fibers, Myostatin levels in VDR−/− SCs from bulk muscles were similar to those of wild type. However, VDR−/− SCs induced to differentiate in culture displayed increased p-Stat3 signaling and Myostatin expression. Finally, VDR−/− mice injected with a Stat3 inhibitor displayed reduced Myostatin expression and function and restored active p70S6K and rpS6 levels, resulting in an amelioration of loss of muscle mass in the soleus muscles.ConclusionsThe loss of muscle mass in slow muscles in the absence of vitamin D signaling is due to elevated levels of phosphorylated Stat3 that leads to an increase in Myostatin signaling, which in turn decreases protein synthesis and fiber size through the phosphorylation of p70S6K and rpS6, respectively.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-017-0121-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor

Gopinath

2017

Skeletal Muscle

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“…Skeletal muscle physiology is critically dependent on the functionality of a progenitor population called, “satellite cells” that proliferate and differentiate to form multinucleated myofibers, thereby contributing to muscle regeneration during injury or exercise 1 – 4 . Conversely, defects in satellite cell function can result in loss of muscle mass and decline in performance that is frequently observed in chronic illnesses and aging 5 . In this aspect, the field of metabolomics has emerged with the intention of providing a comprehensive profile of metabolites and low molecular weight molecules in specific organ tissues, thereby enabling precision medicine and biomarker discovery in various disease states 6 .…”

Section: Introductionmentioning

confidence: 99%

Metabolomic analysis of primary human skeletal muscle cells during myogenic progression

Kumar

Sevak

et al. 2020

Sci Rep

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Skeletal muscle constitutes more than 30% of total body mass using substrates such as glycogen, glucose, free fatty acids, and creatinine phosphate to generate energy. consequently, multinucleated myofibers and resident mononucleated stem cells (satellite cells) generate several metabolites, which enter into circulation affecting the function of other organs, especially during exercise and atrophy. The present study was aimed at building a comprehensive profile of metabolites in primary human skeletal muscle cells during myogenic progression in an untargeted metabolomics approach using a high resolution Orbitrap Fusion Tribrid Mass Spectrometer. Identification of metabolites with multivariate statistical analyses showed a global shift in metabolomic profiles between myoblasts undergoing proliferation and differentiation along with distinctly separable profiles between early and late differentiating cultures. Pathway analyses of 71 unique metabolites revealed that Pantothenate metabolism and coenzyme A biosynthesis and Arginine proline metabolism play dominant roles in proliferating myoblasts, while metabolites involved in vitamin B6, Glyoxylate and Dicarboxylate, Nitrogen, Glutathione, and Tryptophan metabolism were upregulated during differentiation. We found that early and late differentiating cultures displayed differences in Phenylalanine, tyrosine, Glycine, Serine and threonine metabolism. our results identify metabolites during maturation of muscle from progenitor myoblasts that have implications in muscle regeneration and pathophysiology. Skeletal muscle physiology is critically dependent on the functionality of a progenitor population called, "satellite cells" that proliferate and differentiate to form multinucleated myofibers, thereby contributing to muscle regeneration during injury or exercise 1-4. Conversely, defects in satellite cell function can result in loss of muscle mass and decline in performance that is frequently observed in chronic illnesses and aging 5. In this aspect, the field of metabolomics has emerged with the intention of providing a comprehensive profile of metabolites and low molecular weight molecules in specific organ tissues, thereby enabling precision medicine and biomarker discovery in various disease states 6. Thus, identification of metabolic pathways during myogenic progression may provide information on energy requirements of cells during various physiological states of the muscle tissue. Recent studies have characterised the skeletal muscle metabolome during strenuous exercise in humans, neuromuscular diseases such as Pompe disease and Duchenne's muscular dystrophy, daily variations in tissue metabolites vis-à-vis nutritional challenges, overexpression of metabolic regulators, and aging 7-12. Metabolic profiles of young, post-mortem, and aging murine satellite cells have also been evaluated using measurement of mitochondrial function and analysis of metabolic gene signatures associated with different myogenic cell cycle states 13,14. Thus, studies from murine myogenic cell...

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“…In more recent years, several studies have been carried out regarding the involvement of cellular repair systems in the progression of sarcopenia. Muscle fibers are post-mitotic syncytia derived from the fusion of several hundreds of myogenic progenitors [7]. However, not all myogenic precursors differ in muscle fibers during development, a rather small part of them remains in adult muscles forming a pool of undifferentiated stem cells named satellite cells (SCs) which are placed in the adult muscle, between the sarcolemma and the basal lamina surrounding the fiber.…”

Section: The Elderly Muscle Has a Deficit Of Regenerative Processesmentioning

confidence: 99%

“…This complex of events, known as adult myogenesis, maintains the skeletal muscle mass constant. While the relationship between trophic muscle growth and the active role of SCs and/or other pools of adult stem cells as mesangioblasts [72] seems well established [8], much less is known about the possible role played by SCs during the processes leading to muscle atrophy: whether or not there is a role for these cells, is yet to be clarified [7].…”

Section: The Elderly Muscle Has a Deficit Of Regenerative Processesmentioning

confidence: 99%

Molecular and Cellular Aspects of Sarcopenia, Muscle Healthy Aging and Physical Conditioning in the Elderly

Filippo

Bondi

Pietrangelo

et al. 2020

J. of SCI. IN SPORT AND EXERCISE

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During aging, the skeletal muscle tissue is one of the most affected, undergoing loss of mass and function, a process defined as sarcopenia. This age-related muscle mass and function decline, dependent on many factors, predispose individuals to decreased mobility, reduced muscle power and increased risk of falls. Several factors at the cellular and molecular level affect muscle aging, synergizing with each other. At present, it is broadly accepted that Reactive Oxygen Species (ROS) play a primary role in the aging process, especially in those tissues like skeletal muscle, where the generation of free radicals is more pronounced as a consequence of the high consumption of oxygen. Recently, several studies have highlighted the involvement of muscle stem cells (satellite cells, SCs) in the progression of sarcopenia, showing a concomitant regression of activity and number of these cells. At a sub-cellular level, the main processes correlated with sarcopenia are the alteration of protein synthesis and mitochondrial dysfunction. Attempts to slow down or revert sarcopenia are essentially based on three approaches: use of supplements, pharmaceutical therapies and physical activity. In brief, it seems that appropriate physical exercise training protocols could be capable of slowing down and sometimes reversing the sarcopenic process. This finding is the consequence of a beneficial action of physical exercise on mitochondria and/or on the regenerative process led by SCs with different effects on the basis of training characteristics. Furthermore, according to a recent hypothesis, early strength training should be considered as public health advice.

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The quasi-parallel lives of satellite cells and atrophying muscle

Cited by 5 publications

References 223 publications

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor

Metabolomic analysis of primary human skeletal muscle cells during myogenic progression

Molecular and Cellular Aspects of Sarcopenia, Muscle Healthy Aging and Physical Conditioning in the Elderly

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