scholarly journals Deletion of suppressor of cytokine signaling 3 (SOCS3) in muscle stem cells does not alter muscle regeneration in mice after injury

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212880
Author(s):  
Kristy Swiderski ◽  
Marissa K. Caldow ◽  
Timur Naim ◽  
Jennifer Trieu ◽  
Annabel Chee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Muscle Regeneration ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Muscle Stem Cells

scholarly journals The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Aurore L'honoré ◽  
Pierre-Henri Commère ◽  
Elisa Negroni ◽  
Giorgia Pallafacchina ◽  
Bertrand Friguet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Map Kinase ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Redox Regulation ◽  
Primary Cultures ◽  
Rapid Expansion ◽  
Skeletal Muscle Regeneration ◽  
Muscle Stem Cells ◽  
P38α Map Kinase

Skeletal muscle regeneration depends on satellite cells. After injury these muscle stem cells exit quiescence, proliferate and differentiate to regenerate damaged fibres. We show that this progression is accompanied by metabolic changes leading to increased production of reactive oxygen species (ROS). Using Pitx2/3 single and double mutant mice that provide genetic models of deregulated redox states, we demonstrate that moderate overproduction of ROS results in premature differentiation of satellite cells while high levels lead to their senescence and regenerative failure. Using the ROS scavenger, N-Acetyl-Cysteine (NAC), in primary cultures we show that a physiological increase in ROS is required for satellite cells to exit the cell cycle and initiate differentiation through the redox activation of p38α MAP kinase. Subjecting cultured satellite cells to transient inhibition of P38α MAP kinase in conjunction with NAC treatment leads to their rapid expansion, with striking improvement of their regenerative potential in grafting experiments.

scholarly journals Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Manuel Scimeca ◽  
Elena Bonanno ◽  
Eleonora Piccirilli ◽  
Jacopo Baldi ◽  
Alessandro Mauriello ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Stem Cells ◽  
Transmission Electron Microscopy ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Bone Diseases ◽  
Mineral Density ◽  
Muscle Stem Cells ◽  
Age Related ◽  
Transmission Electron

Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed byin situmolecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

scholarly journals Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury

2020 ◽  
Vol 21 (3) ◽  
pp. 932 ◽  
Author(s):  
Piera Filomena Fiore ◽  
Anna Benedetti ◽  
Martina Sandonà ◽  
Luca Madaro ◽  
Marco De Bardi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Muscle Regeneration ◽  
Muscle Wasting ◽  
Expression Level ◽  
Acute Injury ◽  
Mdx Mice ◽  
Muscle Stem Cells ◽  
Advanced Stages ◽  
And Performance ◽  
Dystrophic Mice

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by muscle wasting and chronic inflammation, leading to impaired satellite cells (SCs) function and exhaustion of their regenerative capacity. We previously showed that lack of PKCθ in mdx mice, a mouse model of DMD, reduces muscle wasting and inflammation, and improves muscle regeneration and performance at early stages of the disease. In this study, we show that muscle regeneration is boosted, and fibrosis reduced in mdxθ−/− mice, even at advanced stages of the disease. This phenotype was associated with a higher number of Pax7 positive cells in mdxθ−/− muscle compared with mdx muscle, during the progression of the disease. Moreover, the expression level of Pax7 and Notch1, the pivotal regulators of SCs self-renewal, were upregulated in SCs isolated from mdxθ−/− muscle compared with mdx derived SCs. Likewise, the expression of the Notch ligands Delta1 and Jagged1 was higher in mdxθ−/− muscle compared with mdx. The expression level of Delta1 and Jagged1 was also higher in PKCθ−/− muscle compared with WT muscle following acute injury. In addition, lack of PKCθ prolonged the survival and sustained the differentiation of transplanted myogenic progenitors. Overall, our results suggest that lack of PKCθ promotes muscle repair in dystrophic mice, supporting stem cells survival and maintenance through increased Delta-Notch signaling.

scholarly journals Brief Report: Blockade of Notch Signaling in Muscle Stem Cells Causes Muscular Dystrophic Phenotype and Impaired Muscle Regeneration

Stem Cells ◽  
2013 ◽  
Vol 31 (4) ◽  
pp. 823-828 ◽  
Author(s):  
Shuibin Lin ◽  
Huangxuan Shen ◽  
Baofeng Jin ◽  
Yumei Gu ◽  
Zirong Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Notch Signaling ◽  
Muscle Regeneration ◽  
Muscle Stem Cells

scholarly journals Author response: The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration

2018 ◽  
Author(s):  
Aurore L'honoré ◽  
Pierre-Henri Commère ◽  
Elisa Negroni ◽  
Giorgia Pallafacchina ◽  
Bertrand Friguet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Map Kinase ◽  
Muscle Regeneration ◽  
Redox Regulation ◽  
Author Response ◽  
Muscle Stem Cells ◽  
P38α Map Kinase

scholarly journals Nerve Growth Factor Improves the Muscle Regeneration Capacity of Muscle Stem Cells in Dystrophic Muscle

2006 ◽  
Vol 17 (2) ◽  
pp. 180-192 ◽  
Author(s):  
Mitra Lavasani ◽  
Aiping Lu ◽  
Hairong Peng ◽  
James Cummins ◽  
Johnny Huard
Keyword(s):  
Stem Cells ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Muscle Regeneration ◽  
Regeneration Capacity ◽  
Dystrophic Muscle ◽  
Nerve Growth ◽  
Muscle Stem Cells

Reparative dysfunction during muscle regeneration in Duchenne muscular dystrophy: therapeutic approaches to modulating the muscle environment and muscle stem cells

2019 ◽  
Author(s):  
◽  
Michael Everette Nance
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Regeneration ◽  
Genetic Mutation ◽  
Critical Determinant ◽  
Muscle Stem Cells ◽  
Dystrophin Protein

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Duchenne muscular dystrophy (DMD) is a lethal muscular dystrophy resulting from functional loss of the dystrophin protein, a critical sub-sarcolemmal protein involved in membrane stability. While reparative dysfunction is thought to be a critical determinant of disease progression in humans, regeneration is not significantly impaired in the murine muscular dystrophy (mdx) model. Furthermore, it is not well understood if reparative dysfunction is related to inherent defects in stem cells or chronic alterations in the muscle environment due to disease related remodeling. To address these observed discrepancies, we adapted a whole muscle transplant model to study the in vivo regeneration of intact pieces of skeletal muscle from normal and dystrophic dogs (cDMD), a physiological and clinically relevant model to humans. Regeneration in cDMD muscle grafts was significantly attenuated compared to normal and predisposed to the development of skeletal muscle tumors. We used an adeno-associated virus (AAV) expressing a micro-dystrophin protein to specifically rescue the muscle environment by preventing fiber damage while retaining dystrophin-null SCs. AAV.micro-dystrophin rescued the environment by improving fibrosis, stiffness, and fiber orientation, which significantly improved early muscle regeneration but not late regeneration (2 greater than and less than 4 months post-transplant) via enhancing muscle stem cells differentiation. We next developed Cre- and CRISPR-cas9 gene editing strategies to test the ability of AAV serotype 9 to transduce and treat the genetic mutation in muscle stem cells. We observed efficient SC transduction when used as a single vector expressing Cre. Dual-vector CRISPR-cas9 SC transduction was inefficient and likely related to the requirement for two vectors, promoter usage, and mechanistic differences between Cre-recombination and CRISPR genome editing.

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