Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells.

Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells.
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激活素A-乳腺抑制素系统对衰老的骨骼和肌肉祖细胞的影响。

DOI:
10.1016/j.exger.2012.11.004
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发表时间:
2013-02
影响因子:
3.9
通讯作者:
Hamrick, Mark W.
Hamrick, Mark W.
中科院分区:
医学2区
文献类型:
--
作者:
Bowser, Matthew;Herberg, Samuel;Arounleut, Phonepasong;Shi, Xingming;Fulzele, Sadanand;Hill, William D.;Isales, Carlos M.;Hamrick, Mark W.

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激活素A-肌肉生长抑制素-卵泡抑素系统被认为在整个生长、发育和衰老过程中对肌肉和骨量的调节起重要作用;然而,这些配体对肌肉和骨骼中祖细胞增殖和分化的影响还不清楚。此外,这些因子在肌肉骨骼组织中的相对表达的年龄相关变化尚未被描述。因此,我们使用ELISA检测了C57 BL 6小鼠肌肉和骨骼中激活素A、卵泡抑素和肌生长抑制素(GDF-8)蛋白水平随年龄的变化。然后,我们研究了激活素A,肌肉生长抑制素和卵泡抑素对原代成肌细胞和小鼠骨髓基质细胞(BMSCs)在体外增殖和分化的影响。肌生长抑制素水平和肌生长抑制素:卵泡抑素的比例随着年龄的增长,主要是慢收缩小鼠比目鱼肌,而模式是逆转的快收缩趾长伸肌随着年龄的增长。随着年龄的增长,小鼠骨髓中的肌生长抑制素水平和肌生长抑制素:卵泡抑素比率显著增加(+75%),激活素A水平也是如此(+17%)。卵泡抑素增加了年轻和老年小鼠的原代成肌细胞的增殖,而肌生长抑制素增加了年轻成肌细胞的增殖,但减少了老年成肌细胞的增殖。肌肉生长抑制素以剂量依赖性方式减少年轻和老年BMSCs的增殖,激活素A增加年轻和老年BMSCs的矿化。总之,这些数据表明,小鼠的衰老伴随着激活素A和肌肉生长抑制素表达的变化,以及骨和肌肉祖细胞对这些因子的反应的变化。肌肉生长抑制素似乎在老年小鼠肌肉和骨祖细胞增殖能力受损中发挥特别重要的作用。
The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin: follistatin ratio increased significantly (+75%) in mouse bone marrow with age, as did activin A levels (+17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice.
DOI: 10.1186/1471-2121-9-60
发表时间: 2008-10-28
期刊: BMC cell biology
影响因子: --
作者:
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DOI: 10.1093/gerona/glq109
发表时间: 2010-11-01
影响因子: 5.1
作者:
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DOI: 10.1016/0047-6374(91)90131-i
发表时间: 1991-10-01
影响因子: 5.3
作者:
HOLLOSZY, JO;CHEN, M;YOUNG, JC
通讯作者: YOUNG, JC
DOI: 10.1016/j.exger.2004.08.009
发表时间: 2004-10-01
影响因子: 3.9
作者:
Machida, S;Booth, FW
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DOI: 10.1055/s-2004-831896
发表时间: 2004-08-01
影响因子: 2.7
作者:
Hurwitz, JM;Santoro, N
通讯作者: Santoro, N