scholarly journals The redox-dependent regulation of satellite cells following aseptic muscle trauma (SpEED): Study protocol for a randomized controlled trial

2019 ◽  
Author(s):  
Konstantinos Papanikolaou ◽  
Dimitrios Draganidis ◽  
Athanasios Chatzinikolaou ◽  
Vassiliki C. Laschou ◽  
Kalliopi Georgakouli ◽  
...  

Abstract Background Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. Methods/design Based on their SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated measures design, participants will then receive either Placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for 8 consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2- and 8-days post-exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. Discussion This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial will provide insight into i) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and ii) if skeletal muscle’s potential for regeneration depends on its basal SCs content.

2019 ◽  
Author(s):  
Konstantinos Papanikolaou ◽  
Dimitrios Draganidis ◽  
Athanasios Chatzinikolaou ◽  
Vassiliki C. Laschou ◽  
Kalliopi Georgakouli ◽  
...  

Abstract Background Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. Methods/design Based on their SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated measures design, participants will then receive either Placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for 8 consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2- and 8-days post-exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. Discussion This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial will provide insight into i) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and ii) if skeletal muscle’s potential for regeneration depends on its basal SCs content.


2019 ◽  
Author(s):  
Konstantinos Papanikolaou ◽  
Dimitrios Draganidis ◽  
Athanasios Chatzinikolaou ◽  
Vassiliki C. Laschou ◽  
Kalliopi Georgakouli ◽  
...  

Abstract Background Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. Methods/design Based on their SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated measures design, participants will then receive either Placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for 8 consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2- and 8-days post-exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. Discussion This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial will provide insight into i) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and ii) if skeletal muscle’s potential for regeneration depends on its basal SCs content.


2019 ◽  
Author(s):  
Konstantinos Papanikolaou ◽  
Athanasios Z. Jamurtas ◽  
Dimitrios Draganidis ◽  
Athanasios Chatzinikolaou ◽  
Vassiliki C. Laschou ◽  
...  

Abstract Background: Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. Methods: Based on their SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated measures design, participants will then receive either Placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for 8 consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2- and 8-days post-exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. Discussion: This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial will provide insight into i) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and ii) if skeletal muscle’s potential for regeneration depends on its basal SCs content. Trial registration: ClinicalTrials.gov, NCT03711838; Registered on 10/19/2018. Keywords: Muscle stem cells, cell signaling, antioxidants, redox potential, tissue regeneration.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1479
Author(s):  
Karolina Archacka ◽  
Joanna Bem ◽  
Edyta Brzoska ◽  
Areta M. Czerwinska ◽  
Iwona Grabowska ◽  
...  

Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.


2019 ◽  
Vol 48 (1) ◽  
pp. 54-66 ◽  
Author(s):  
Katherine Newman-Taylor ◽  
Pamela McSherry ◽  
Lusia Stopa

AbstractBackground:Paranoia is often accompanied by distressing intrusions associated with traumatic memories, yet one of the best-evidenced interventions, imagery rescripting (IR), is not routinely offered. This is likely to be due to poor understanding of the effects of IR on postulated mechanisms of change as well as the absence of a robust evidence base.Aims:This study aimed to establish proof of principle that IR impacts key cognitive-affective processes associated with distressing intrusions – memory characteristics and self-representations – and level of paranoia.Method:We used a within-subject repeated measures design to examine the effect of single-session IR on memory characteristics (level of intrusions, vividness, distress, encapsulated belief strength, emotion intensity and frequency), self-representation variables, affect and paranoia. Fifteen participants were seen once before and once after the IR session, to gather baseline and follow-up data.Results:As predicted, participants reported reductions in memory characteristics, improved self-esteem and positive affect, and reduced negative affect and paranoia, with large effect sizes. These effects were maintained at follow-up.Conclusions:While a within-subject design is useful for initial exploration of novel interventions, controlled studies are needed to determine causality. This is the first study to examine mechanisms of IR in paranoia. A controlled trial is now warranted.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Josiane Joseph ◽  
Jason D. Doles

AbstractMany chronic disease patients experience a concurrent loss of lean muscle mass. Skeletal muscle is a dynamic tissue maintained by continuous protein turnover and progenitor cell activity. Muscle stem cells, or satellite cells, differentiate (by a process called myogenesis) and fuse to repair and regenerate muscle. During myogenesis, satellite cells undergo extensive metabolic alterations; therefore, pathologies characterized by metabolic derangements have the potential to impair myogenesis, and consequently exacerbate skeletal muscle wasting. How disease-associated metabolic disruptions in satellite cells might be contributing to wasting is an important question that is largely neglected. With this review we highlight the impact of various metabolic disruptions in disease on myogenesis and skeletal muscle regeneration. We also discuss metabolic therapies with the potential to improve myogenesis, skeletal muscle regeneration, and ultimately muscle mass.


2018 ◽  
Vol 315 (5) ◽  
pp. C714-C721 ◽  
Author(s):  
Irena A. Rebalka ◽  
Cynthia M. F. Monaco ◽  
Nina E. Varah ◽  
Thorsten Berger ◽  
Donna M. D’souza ◽  
...  

Lipocalin-2 (LCN2) is an adipokine previously described for its contribution to numerous processes, including innate immunity and energy metabolism. LCN2 has also been demonstrated to be an extracellular matrix (ECM) regulator through its association with the ECM protease matrix metalloproteinase-9 (MMP-9). With the global rise in obesity and the associated comorbidities related to increasing adiposity, it is imperative to gain an understanding of the cross talk between adipose tissue and other metabolic tissues, such as skeletal muscle. Given the function of LCN2 on the ECM in other tissues and the importance of matrix remodeling in skeletal muscle regeneration, we examined the localization and expression of LCN2 in uninjured and regenerating wild-type skeletal muscle and assessed the impact of LCN2 deletion (LCN2−/−) on skeletal muscle repair following cardiotoxin injury. Though LCN2 was minimally present in uninjured skeletal muscle, its expression was increased significantly at 1 and 2 days postinjury, with expression present in Pax7-positive satellite cells. Although satellite cell content was unchanged, the ability of quiescent satellite cells to become activated was significantly impaired in LCN2−/− skeletal muscles. Skeletal muscle regeneration was also significantly compromised as evidenced by decreased embryonic myosin heavy chain expression and smaller regenerating myofiber areas. Consistent with a role for LCN2 in MMP-9 regulation, regenerating muscle also displayed a significant increase in fibrosis and lower ( P = 0.07) MMP-9 activity in LCN2−/− mice at 2 days postinjury. These data highlight a novel role for LCN2 in muscle regeneration and suggest that changes in adipokine expression can significantly impact skeletal muscle repair.


1966 ◽  
Vol 53 (7) ◽  
pp. 638-642 ◽  
Author(s):  
J. C. T. Church ◽  
R. F. X. Noronha ◽  
D. B. Allbrook

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tannaz Norizadeh Abbariki ◽  
Zita Gonda ◽  
Denise Kemler ◽  
Pavel Urbanek ◽  
Tabea Wagner ◽  
...  

AbstractThe process of myogenesis which operates during skeletal muscle regeneration involves the activation of muscle stem cells, the so-called satellite cells. These then give rise to proliferating progenitors, the myoblasts which subsequently exit the cell cycle and differentiate into committed precursors, the myocytes. Ultimately, the fusion of myocytes leads to myofiber formation. Here we reveal a role for the transcriptional co-regulator nTRIP6, the nuclear isoform of the LIM-domain protein TRIP6, in the temporal control of myogenesis. In an in vitro model of myogenesis, the expression of nTRIP6 is transiently up-regulated at the transition between proliferation and differentiation, whereas that of the cytosolic isoform TRIP6 is not altered. Selectively blocking nTRIP6 function results in accelerated early differentiation followed by deregulated late differentiation and fusion. Thus, the transient increase in nTRIP6 expression appears to prevent premature differentiation. Accordingly, knocking out the Trip6 gene in satellite cells leads to deregulated skeletal muscle regeneration dynamics in the mouse. Thus, dynamic changes in nTRIP6 expression contributes to the temporal control of myogenesis.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3028
Author(s):  
Paulina Roux-Biejat ◽  
Marco Coazzoli ◽  
Pasquale Marrazzo ◽  
Silvia Zecchini ◽  
Ilaria Di Renzo ◽  
...  

Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery.


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