Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion
| Autor: | Takashi Matsuwaki, Hidetoshi Sugihara, Masugi Nishihara, Keitaro Yamanouchi, Naomi Teramoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Senescence Male Aging Sarcopenia senescence Adipose tissue Muscle Development Myoblasts 03 medical and health sciences Myoblast fusion 0302 clinical medicine Downregulation and upregulation medicine Adipocytes Myocyte Animals Progenitor cell skeletal muscle Rats Wistar Cellular Senescence Adipogenesis Chemistry Mesenchymal stem cell Skeletal muscle Cell Differentiation Mesenchymal Stem Cells Cell Biology differentiation Fibroblasts Cell biology Rats Oxidative Stress 030104 developmental biology medicine.anatomical_structure ageing 030217 neurology & neurosurgery Research Paper mesenchymal progenitor cell |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Sarcopenia is the age-related loss of skeletal muscle mass and function. Skeletal muscle comprises diverse progenitor cells, including mesenchymal progenitor cells (MPCs), which normally support myogenic cell function but cause a decline in skeletal muscle function after differentiating into fibrous/adipose tissue. Cellular senescence is a form of persistent cell cycle arrest caused by cellular stress, including oxidative stress, and is accompanied by the acquisition of senescence-associated secretory phenotype (SASP). Here, we found γH2AX+ senescent cells appeared in the interstitium in skeletal muscle, corresponding in position to that of MPCs. H2O2 mediated oxidative stress in 2G11 cells, a rat MPC clone previously established in our laboratory, successfully induced senescence, as shown by the upregulation of p21 and SASP factors, including IL-6. The senescent 2G11 cells lost their fibro/adipogenic potential, but, intriguingly, coculture of myoblasts with senescent 2G11 cells abrogated the myotube formation, which coincided with the downregulation of myomaker, a muscle-specific protein involved in myogenic cell fusion; however, forced expression of myomaker could not rescue this abrogation. These results suggest that senescent MPCs in aged rat skeletal muscle lose their fibro/adipogenic potential, but differ completely from undifferentiated progenitor cells in that senescent MPCs suppress myoblast fusion and thereby potentially accelerate sarcopenia. |
| Databáze: | OpenAIRE |
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