Stimulation of Non-canonical NF-κB Through Lymphotoxin-β-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle

Myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle are cellular processes under tight control of various signaling pathways. Here, we investigated the role of non-canonical NF-κB signaling in myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle. We stimulated non-canonical NF-κB signaling with an agonistically acting antibody of the lymphotoxin beta receptor (LTβR). Interestingly, we found that stimulation of non-canonical NF-κB signaling through the LTβR agonist impairs myogenic differentiation, muscle stem cell function, and regeneration of skeletal muscle. Furthermore, we show that stimulation of non-canonical NF-κB signaling by the LTβR agonist coincides with activation of canonical NF-κB signaling. We suggest a direct crosstalk between canonical and non-canonical NF-κB signaling during myogenic differentiation which is required for proper myogenic differentiation and thereby regeneration of skeletal muscle.

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Age and prior exercise in vivo determine the subsequent in vitro molecular profile of myoblasts and nonmyogenic cells derived from human skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00049.2019 ◽

2019 ◽

Vol 316 (6) ◽

pp. C898-C912 ◽

Cited By ~ 7

Author(s):

Cecilie J. L. Bechshøft ◽

Simon M. Jensen ◽

Peter Schjerling ◽

Jesper L. Andersen ◽

Rene B. Svensson ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cell ◽

Human Skeletal Muscle ◽

Cell Function ◽

Myogenic Differentiation ◽

Molecular Profile ◽

Muscle Stem Cell ◽

Myogenic Cells

The decline in skeletal muscle regenerative capacity with age is partly attributed to muscle stem cell (satellite cell) dysfunction. Recent evidence has pointed to a strong interaction between myoblasts and fibroblasts, but the influence of age on this interaction is unknown. Additionally, while the native tissue environment is known to determine the properties of myogenic cells in vitro, how the aging process alters this cell memory has not been established at the molecular level. We recruited 12 young and 12 elderly women, who performed a single bout of heavy resistance exercise with the knee extensor muscles of one leg. Five days later, muscle biopsies were collected from both legs, and myogenic cells and nonmyogenic cells were isolated for in vitro experiments with mixed or separated cells and analyzed by immunostaining and RT-PCR. A lower myogenic fusion index was detected in the cells from the old versus young women, in association with differences in gene expression levels of key myogenic regulatory factors and senescence, which were further altered by performing exercise before tissue sampling. Coculture with nonmyogenic cells from the elderly led to a higher myogenic differentiation index compared with nonmyogenic cells from the young. These findings show that the in vitro phenotype and molecular profile of human skeletal muscle myoblasts and fibroblasts is determined by the age and exercise state of the original in vivo environment and help explain how exercise can enhance muscle stem cell function in old age.

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

The Indonesian Biomedical Journal ◽

10.18585/inabj.v7i2.73 ◽

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

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