Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion.
Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion.
复制标题
DOI：
10.18632/aging.101425
复制
发表时间：
2018-04-25
期刊：
影响因子：
--
通讯作者：
Nishihara M
中科院分区：
文献类型：
--
作者：
Sugihara H;Teramoto N;Yamanouchi K;Matsuwaki T;Nishihara M
骨骼肌减少症是与年龄有关的骨骼肌质量和功能的丧失。骨骼肌由多种祖细胞组成，包括间充质祖细胞（MPCs），其通常支持肌细胞功能，但在分化为纤维/脂肪组织后导致骨骼肌功能下降。细胞衰老是由细胞应激（包括氧化应激）引起的持续细胞周期停滞的一种形式，并伴随着衰老相关分泌表型（SASP）的获得。我们发现，骨骼肌间质中出现了γ - h2ax +衰老细胞，其位置与MPCs相对应。H2O2介导的氧化应激在我们实验室之前建立的大鼠MPC克隆2G11细胞中成功诱导衰老，这表明p21和SASP因子，包括IL-6的上调。衰老的2G11细胞失去了成纤维/脂肪的潜能，但有趣的是，成肌细胞与衰老的2G11细胞共培养消除了肌管的形成，这与myomaker（一种参与成肌细胞融合的肌肉特异性蛋白）的下调相一致；然而，我的立法者强行表达并不能挽救这一废除。这些结果表明，衰老大鼠骨骼肌中衰老的MPCs失去了其纤维/脂肪生成的潜力，但与未分化的祖细胞完全不同，衰老的MPCs抑制成肌细胞融合，从而可能加速肌肉减少。
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.
登录
查看更多内容
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
82.9
作者：
Bonci, Desiree;Coppola, Valeria;De Maria, Ruggero
通讯作者：
De Maria, Ruggero
影响因子：
5.6
作者：
Luo W;Li E;Nie Q;Zhang X
通讯作者：
Zhang X
DOI：
10.1038/nrrheum.2017.60
发表时间：
2017-06
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Dennison EM;Sayer AA;Cooper C
通讯作者：
Cooper C
影响因子：
4.9
作者：
Mann CJ;Perdiguero E;Kharraz Y;Aguilar S;Pessina P;Serrano AL;Muñoz-Cánoves P
通讯作者：
Muñoz-Cánoves P