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 ◽  
...  

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.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Aurore L'honoré ◽  
Pierre-Henri Commère ◽  
Elisa Negroni ◽  
Giorgia Pallafacchina ◽  
Bertrand Friguet ◽  
...  

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.


Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 171 ◽  
Author(s):  
Vladyslava Rybka ◽  
Yuichiro J. Suzuki ◽  
Alexander S. Gavrish ◽  
Vyacheslav A. Dibrova ◽  
Sergiy G. Gychka ◽  
...  

The brain is sensitive to aging-related morphological changes, where many neurodegenerative diseases manifest accompanied by a reduction in memory. The hippocampus is especially vulnerable to damage at an early stage of aging. The present transmission electron microscopy study examined the synapses and synaptic mitochondria of the CA1 region of the hippocampal layer in young-adult and old rats by means of a computer-assisted image analysis technique. Comparing young-adult (10 months of age) and old (22 months) male Fischer (CDF) rats, the total numerical density of synapses was significantly lower in aged rats than in the young adults. This age-related synaptic loss involved degenerative changes in the synaptic architectonic organization, including damage to mitochondria in both pre- and post-synaptic compartments. The number of asymmetric synapses with concave curvature decreased with age, while the number of asymmetric synapses with flat and convex curvatures increased. Old rats had a greater number of damaged mitochondria in their synapses, and most of this was type II and type III mitochondrial structural damage. These results demonstrate age-dependent changes in the morphology of synaptic mitochondria that may underlie declines in age-related synaptic function and may couple to age-dependent loss of synapses.


Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 183 ◽  
Author(s):  
David Lee ◽  
Akshay Bareja ◽  
David Bartlett ◽  
James White

Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of sarcopenia, prolonged hospitalization, and loss of autonomy. Although several age-sensitive pathways have been identified, further investigation is needed to define targets of cellular dysfunction. Autophagy, a process of cellular catabolism, is emerging as a key regulator of muscle regeneration affecting stem cell, immune cell, and myofiber function. Muscle stem cell senescence is associated with a suppression of autophagy during key phases of the regenerative program. Macrophages, a key immune cell involved in muscle repair, also rely on autophagy to aid in tissue repair. This review will focus on the role of autophagy in various aspects of the regenerative program, including adult skeletal muscle stem cells, monocytes/macrophages, and corresponding age-associated dysfunction. Furthermore, we will highlight rejuvenation strategies that alter autophagy to improve muscle regenerative function.


2020 ◽  
Author(s):  
James S. Novak ◽  
Davi A.G. Mázala ◽  
Marie Nearing ◽  
Nayab F. Habib ◽  
Tessa Dickson ◽  
...  

AbstractAge-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle micro-environment such as to disfavor the myogenic function of these cells.


2014 ◽  
Vol 5 ◽  
pp. 1732-1737 ◽  
Author(s):  
Michal Babič ◽  
Daniel Horák ◽  
Lyubov L Lukash ◽  
Tetiana A Ruban ◽  
Yurii N Kolomiets ◽  
...  

Surface-modified maghemite (γ-Fe2O3) nanoparticles were obtained by using a conventional precipitation method and coated with D-mannose and poly(N,N-dimethylacrylamide). Both the initial and the modified particles were characterized by transmission electron microscopy and dynamic light scattering with regard to morphology, particle size and polydispersity. In vitro survival of human stem cells was then investigated by using the methyl thiazolyl tetrazolium (MTT) assay, which showed that D-mannose- and poly(N,N-dimethylacrylamide)-coated γ-Fe2O3 particles exhibit much lower level of cytotoxicity than the non-coated γ-Fe2O3.


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