Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.
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DOI:
10.1186/s13395-017-0132-z
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发表时间:
2017-07-10
期刊:
影响因子:
4.9
通讯作者:
Peterson CA
Peterson CA
中科院分区:
医学2区
文献类型:
--
作者:
Murach KA;White SH;Wen Y;Ho A;Dupont-Versteegden EE;McCarthy JJ;Peterson CA

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Pax 7+卫星细胞是小鼠出生后发育过程中骨骼肌纤维生长所必需的。卫星细胞介导的肌层增生似乎也持续到成年早期。鉴于卫星细胞在肌肉发育过程中的重要作用,我们假设卫星细胞适应肥大刺激的必要性取决于成熟年龄。在2个月龄(年轻)和4个月龄(成熟)时,用媒介物(卫星细胞充满,SC+)或他莫昔芬(卫星细胞耗尽,SC-)处理Pax 7 CreER-R26 RDTA小鼠5天。在2周洗脱后,使小鼠经受假手术或10天足底的电消融超负荷(每组n = 6-9)。手术方法最大限度地减少再生,从头纤维形成和纤维分裂,同时促进肌纤维生长。通过免疫组织化学评价卫星细胞密度(Pax 7+细胞/纤维)、胚胎肌球蛋白重链表达(eMyHC)和肌纤维横截面积(CSA)。在分离的单个肌纤维上计数肌核(肌核/100 mm)。他莫昔芬治疗使卫星细胞消耗≥90%,并防止了年轻和成熟小鼠中肌层过度增生(p < 0.05)。超负荷后SC-小鼠的卫星细胞没有恢复。在年轻SC+(p = 0.07)、成熟SC+(p < 0.05)和成熟SC-小鼠(p <0.05)中,平均肌纤维CSA增加~20%。相比之下,年轻的SC-小鼠的肌纤维肥大得到了预防.肌纤维数量仅在过载后的成熟小鼠中增加(p < 0.05),并且eMyHC表达是可变的,特别是在成熟SC+小鼠中。过载诱导的肥大对卫星细胞的依赖于成熟年龄,并且年轻小鼠与成熟小鼠对过载的整体反应不同。本文的在线版本(doi:10.1186/s13395-017-0132-z)包含补充材料,可供授权用户使用。
Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6–9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p < 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05), and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p < 0.05), and eMyHC expression was variable, specifically in mature SC+ mice. Reliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice. The online version of this article (doi:10.1186/s13395-017-0132-z) contains supplementary material, which is available to authorized users.
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