scholarly journals Dysregulated cell signalling and reduced satellite cell potential in ageing muscle

2019 ◽  
Author(s):  
Ketan Patel ◽  
Biggy Simbi ◽  
Olli Ritvos ◽  
Sakthivel Vaiyapuri ◽  
Gurtej K Dhoot
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Development ◽  
Myogenic Differentiation ◽  
Cell Signalling ◽  
Muscle Fibres ◽  
Proliferative Potential ◽  
Wnt Proteins ◽  
Age Related

ABSTRACTAberrant activation of signalling pathways has been postulated to promote age related changes in skeletal muscle. Cell signalling activation requires not only the expression of ligands and receptors but also an appropriate environment that facilitates their interaction. Here we first examined the expression of SULF1/SULF2 and members of RTK and the Wnt family in skeletal muscle of normal and a mouse model of accelerated ageing. We show that SULF1/SULF2 and these signalling components, a feature of early muscle development are barely detectable in early postnatal muscle. Real time qPCR and immunocytochemical analysis showed gradual but progressive up-regulation of SULF1/SULF2 and RTK/Wnt proteins not only in the activated satellite cells but also on muscle fibres that gradually increased with age. Satellite cells on isolated muscle fibres showed spontaneous in vivo satellite cell activation and progressive reduction in proliferative potential and responsiveness to HGF and dysregulated myogenic differentiation with age. Finally, we show that SULF1/SULF2 and RTK/Wnt signalling components are expressed in progeric mouse muscles at earlier stage but their expression is attenuated by an intervention that promotes muscle repair and growth.

scholarly journals Metformin Delays Satellite Cell Activation and Maintains Quiescence

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Theodora Pavlidou ◽  
Milica Marinkovic ◽  
Marco Rosina ◽  
Claudia Fuoco ◽  
Simone Vumbaca ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Cell Activation ◽  
Myogenic Differentiation ◽  
Metabolic State ◽  
Cell Pool ◽  
Age Related ◽  
Satellite Cell Activation

The regeneration of the muscle tissue relies on the capacity of the satellite stem cell (SC) population to exit quiescence, divide asymmetrically, proliferate, and differentiate. In age-related muscle atrophy (sarcopenia) and several dystrophies, regeneration cannot compensate for the loss of muscle tissue. These disorders are associated with the depletion of the satellite cell pool or with the loss of satellite cell functionality. Recently, the establishment and maintenance of quiescence in satellite cells have been linked to their metabolic state. In this work, we aimed to modulate metabolism in order to preserve the satellite cell pool. We made use of metformin, a calorie restriction mimicking drug, to ask whether metformin has an effect on quiescence, proliferation, and differentiation of satellite cells. We report that satellite cells, when treated with metformin in vitro, ex vivo, or in vivo, delay activation, Pax7 downregulation, and terminal myogenic differentiation. We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway. Moreover, in vivo administration of metformin induces a belated regeneration of cardiotoxin- (CTX-) damaged skeletal muscle. Interestingly, satellite cells treated with metformin immediately after isolation are smaller in size and exhibit reduced pyronin Y levels, which suggests that metformin-treated satellite cells are transcriptionally less active. Thus, our study suggests that metformin delays satellite cell activation and differentiation by favoring a quiescent, low metabolic state.

Shift from slow- to fast-twitch muscle fibres in skeletal muscle of newborn heterozygous and homozygous myostatin-knockout piglets

2019 ◽  
Vol 31 (10) ◽  
pp. 1628 ◽  
Author(s):  
Mei-Fu Xuan ◽  
Zhao-Bo Luo ◽  
Jun-Xia Wang ◽  
Qing Guo ◽  
Sheng-Zhong Han ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Muscle Development ◽  
Transforming Growth Factor ◽  
Myogenic Differentiation ◽  
Muscle Fibres ◽  
Skeletal Muscle Development ◽  
Cross Sectional ◽  
Gene And Protein Expression ◽  
Fast Twitch

Myostatin (MSTN) is a member of the transforming growth factor-β superfamily that negatively regulates skeletal muscle development. A lack of MSTN induces muscle hypertrophy and increases formation of fast-twitch (Type II) muscle fibres. This study investigated muscle development in newborn heterozygous (MSTN+/−) and homozygous (MSTN−/−) MSTN-knockout piglets. Detailed morphological and gene and protein expression analyses were performed of the biceps femoris, semitendinosus and diaphragm of MSTN+/−, MSTN−/− and wild-type (WT) piglets. Haematoxylin–eosin staining revealed that the cross-sectional area of muscle fibres was significantly larger in MSTN-knockout than WT piglets. ATPase staining demonstrated that the percentage of Type IIb and IIa muscle fibres was significantly higher in MSTN−/− and MSTN+/− piglets respectively than in WT piglets. Western blotting showed that protein expression of myosin heavy chain-I was reduced in muscles of MSTN-knockout piglets. Quantitative reverse transcription–polymerase chain reaction revealed that, compared with WT piglets, myogenic differentiation factor (MyoD) mRNA expression in muscles was 1.3- to 2-fold higher in MSTN+/− piglets and 1.8- to 3.5-fold higher MSTN−/− piglets (P<0.05 and P<0.01 respectively). However, expression of myocyte enhancer factor 2C (MEF2C) mRNA in muscles was significantly lower in MSTN+/− than WT piglets (P<0.05). MSTN plays an important role in skeletal muscle development and regulates muscle fibre type by modulating the gene expression of MyoD and MEF2C in newborn piglets.

scholarly journals Stem cells for skeletal muscle repair

2011 ◽  
Vol 366 (1575) ◽  
pp. 2297-2306 ◽  
Author(s):  
Jennifer L. Shadrach ◽  
Amy J. Wagers
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Muscle Disease ◽  
Muscle Fibres ◽  
Muscle Repair ◽  
Muscle Satellite Cells

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.

scholarly journals Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

Satellite cell proliferation and differentiation during postnatal growth of porcine skeletal muscle

2002 ◽  
Vol 282 (4) ◽  
pp. C899-C906 ◽  
Author(s):  
N. T Mesires ◽  
M. E. Doumit
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Nuclear Antigen ◽  
Positive Staining ◽  
Age Related ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Satellite Cell Proliferation

Age-related changes in satellite cell proliferation and differentiation during rapid growth of porcine skeletal muscle were examined. Satellite cells were isolated from hindlimb muscles of pigs at 1, 7, 14, and 21 wk of age (4 animals/age group). Satellite cells were separated from cellular debris by using Percoll gradient centrifugation and were adsorbed to glass coverslips for fluorescent immunostaining. Positive staining for neural cell adhesion molecule (NCAM) distinguished satellite cells from nonmyogenic cells. The proportion of NCAM-positive cells (satellite cells) in isolates decreased from 1 to 7 wk of age. Greater than 77% of NCAM-positive cells were proliferating cell nuclear antigen positive at all ages studied. Myogenin-positive satellite cells decreased from 30% at 1 wk to 14% at 7 wk of age and remained at constant levels thereafter. These data indicate that a high percentage of satellite cells remain proliferative during rapid postnatal muscle growth. The reduced proportion of myogenin-positive cells during growth may reflect a decrease in the proportion of differentiating satellite cells or accelerated incorporation of myogenin-positive cells into myofibers.

Myonuclear accretion is a major determinant of avian skeletal muscle growth

1997 ◽  
Vol 272 (2) ◽  
pp. C565-C571 ◽  
Author(s):  
P. E. Mozdziak ◽  
E. Schultz ◽  
R. G. Cassens
Keyword(s):  
Skeletal Muscle ◽  
Mitotic Activity ◽  
Satellite Cell ◽  
Muscle Development ◽  
Muscle Growth ◽  
Growth Potential ◽  
Unit Size ◽  
Skeletal Muscle Growth ◽  
Age Related ◽  
Related Increase

The role of satellite cells and DNA unit size in determining skeletal muscle growth was studied after mitotic activity was inhibited in the left pectoralis thoracicus of 2-wk-old tom turkeys by means of a 25-Gy dose of irradiation. Toms were killed and muscle weights were obtained 1 (n = 5), 4 (n = 6), 7 (n = 6), and 15 (n = 4) wk after irradiation. Satellite cell mitotic activity and DNA unit size were determined using enzymatically isolated myofiber segments and image analysis. Irradiated and nonirradiated muscle weights increased (P < 0.01) between all ages examined, but irradiated muscle weights were significantly (P < 0.01) lower than nonirradiated muscle weights at 4, 7, and 15 wk after irradiation. Satellite cell mitotic activity was lower (P < 0.01) in irradiated than in nonirradiated muscles at 1 and 4 wk after irradiation and resulted in a significant reduction (P < 0.05) in the number of myofiber nuclei per millimeter at 4 and 7 wk after irradiation. Satellite cell mitotic activity was higher (P < 0.05) in irradiated than in nonirradiated muscles at 7 wk after irradiation, but at 15 wk after irradiation it had fallen to low levels in both muscles. There was no significant (P > 0.10) difference in DNA unit size between muscles at any time, but there was an age-related increase (P < 0.01) for both muscles. Irradiation reduced muscle growth through a transient reduction in myonuclear production at a critical time (3-6 wk of age) in posthatch skeletal muscle development. The age-related increase in DNA unit size was not accelerated to compensate for the reduction in myonuclear accretion. Thus it appears that muscle growth potential is governed mostly by myonuclear accretion and to a lesser extent by DNA unit size.

scholarly journals KDM4A regulates myogenesis by demethylating H3K9me3 of myogenic regulatory factors

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Qi Zhu ◽  
Feng Liang ◽  
Shufang Cai ◽  
Xiaorong Luo ◽  
Tianqi Duo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Satellite Cells ◽  
Muscle Development ◽  
Kinase Inhibitor ◽  
Myogenic Differentiation ◽  
Myoblast Differentiation ◽  
Proliferation And Differentiation ◽  
H3k9me3 Level

AbstractHistone lysine demethylase 4A (KDM4A) plays a crucial role in regulating cell proliferation, cell differentiation, development and tumorigenesis. However, little is known about the function of KDM4A in muscle development and regeneration. Here, we found that the conditional ablation of KDM4A in skeletal muscle caused impairment of embryonic and postnatal muscle formation. The loss of KDM4A in satellite cells led to defective muscle regeneration and blocked the proliferation and differentiation of satellite cells. Myogenic differentiation and myotube formation in KDM4A-deficient myoblasts were inhibited. Chromatin immunoprecipitation assay revealed that KDM4A promoted myogenesis by removing the histone methylation mark H3K9me3 at MyoD, MyoG and Myf5 locus. Furthermore, inactivation of KDM4A in myoblasts suppressed myoblast differentiation and accelerated H3K9me3 level. Knockdown of KDM4A in vitro reduced myoblast proliferation through enhancing the expression of the cyclin-dependent kinase inhibitor P21 and decreasing the expression of cell cycle regulator Cyclin D1. Together, our findings identify KDM4A as an important regulator for skeletal muscle development and regeneration, orchestrating myogenic cell proliferation and differentiation.

Recent Developments in Breast Muscle Myopathies Associated with Growth in Poultry

2019 ◽  
Vol 7 (1) ◽  
pp. 289-308 ◽  
Author(s):  
Sandra G. Velleman
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Satellite Cell ◽  
Meat Quality ◽  
Satellite Cells ◽  
Muscle Development ◽  
Growth Function ◽  
Repair Process ◽  
Breast Muscle ◽  
Cellular Mechanisms

The functional unit in skeletal muscle is the multinucleated myofiber, which is composed of parallel arrays of microfibrils. The myofiber and sarco-mere structure of skeletal muscle are established during embryogenesis, when mononuclear myoblast cells fuse to form multinucleated myotubes and develop into muscle fibers. With the myoblasts permanently unable to enter a proliferative state again after they fuse to form the multinucleated myotube, postnatal myofiber growth, muscle homeostasis, and myofiber regeneration are dependent on a myogenic stem cell, the satellite cell. Because the satellite cell is a partially differentiated stem cell controlling the state of skeletal muscle structure throughout the life of the bird, it can impact muscle development and structure, growth, and regeneration and, subsequently, meat quality. When myofibers are damaged, muscle repair is dependent on the satellite cells. Regenerated myofibers after the repair process should be similar to the original muscle fiber. Despite significant improvements in meat-type birds, degenerative myopathies have arisen. In many of these degenerative breast muscle myopathies, like Wooden Breast, satellite cell–mediated regeneration of muscle is suppressed. Thus, the biological function of avian myogenic satellite cells and their influence on cellular mechanisms affecting breast muscle development and growth, function during degenerative myopathies, and meat quality are discussed.

scholarly journals An Overview About the Biology of Skeletal Muscle Satellite Cells

2019 ◽  
Vol 20 (1) ◽  
pp. 24-37 ◽  
Author(s):  
Laura Forcina ◽  
Carmen Miano ◽  
Laura Pelosi ◽  
Antonio Musarò
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Cell Biology ◽  
Regulatory Networks ◽  
Myogenic Differentiation ◽  
Cell Activity ◽  
Quiescent State

The peculiar ability of skeletal muscle tissue to operate adaptive changes during post-natal development and adulthood has been associated with the existence of adult somatic stem cells. Satellite cells, occupying an exclusive niche within the adult muscle tissue, are considered bona fide stem cells with both stem-like properties and myogenic activities. Indeed, satellite cells retain the capability to both maintain the quiescence in uninjured muscles and to be promptly activated in response to growth or regenerative signals, re-engaging the cell cycle. Activated cells can undergo myogenic differentiation or self-renewal moving back to the quiescent state. Satellite cells behavior and their fate decision are finely controlled by mechanisms involving both cell-autonomous and external stimuli. Alterations in these regulatory networks profoundly affect muscle homeostasis and the dynamic response to tissue damage, contributing to the decline of skeletal muscle that occurs under physio-pathologic conditions. Although the clear myogenic activity of satellite cells has been described and their pivotal role in muscle growth and regeneration has been reported, a comprehensive picture of inter-related mechanisms guiding muscle stem cell activity has still to be defined. Here, we reviewed the main regulatory networks determining satellite cell behavior. In particular, we focused on genetic and epigenetic mechanisms underlining satellite cell maintenance and commitment. Besides intrinsic regulations, we reported current evidences about the influence of environmental stimuli, derived from other cell populations within muscle tissue, on satellite cell biology.

Skeletal Muscle Regeneration: MSC versus Satellite Cells

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P86-P86
Author(s):  
Jens Stern-Straeter ◽  
Juritz Stephanie ◽  
Gregor Bran ◽  
Frank Riedel ◽  
Haneen Sadick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Cell Cultures ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Myogenic Differentiation ◽  
Culture Conditions ◽  
Muscle Biopsies

Problem Differentiating stem cells into the myogenic linage in order to create functional muscle tissue is a challenging endeavour. In this work, adipose-derived mesenchymal stem cells (MSC) and satellite cells derived from muscle biopsies were compared regarding proliferation and myogenic differentiation potential under standardized cell culture conditions. This data was obtained in order to discover the most promising type of stem cell for regeneration of muscle tissue and to determine the optimal culture conditions for later clinical use. Methods Human MSC were isolated from adipose tissue, and primary human skeletal myoblasts were extracted from muscle biopsies by enzymatic digestion. Proliferation was analysed using the AlamarBlue® assay. Gene expression of marker genes – such as Myogenin, Myo D, Myf 5 and MHC – were analysed by RT-PCR. Immunostainings against desmin and sarcomeric-actin were performed as differentiation markers. Results MSC cell cultures showed a greater proliferation rate compared with satellite cell cultures. In both stem cell cultures, myogenic differentiation/heritage could be verified by immunostainings against the muscle-specific marker desmin. Gene expression and protein analysis revealed a more stable differentiation of human satellite cell cultures. Conclusion Characterization of both human MSC cultures and satellite cell cultures – and thereby an understanding of myogenesis – might lead to their clinical usage in skeletal muscle tissue engineering. The results in this study appear to indicate that human satellite cell cultures have a more stable differentiation under in vitro conditions and that they might offer a greater potential for skeletal muscle tissue engineering purposes. Significance Our study contributes to the understanding of myogenic differentiation of MSC and satellite cells and helps to improve culture systems for later clinical utilization.

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