Mechanical activation of β-catenin regulates phenotype in adult murine marrow-derived mesenchymal stem cells.
Mechanical activation of β-catenin regulates phenotype in adult murine marrow-derived mesenchymal stem cells.
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DOI：
10.1002/jor.21156
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发表时间：
2010-11
影响因子：
2.8
通讯作者：
Rubin, Janet
中科院分区：
文献类型：
--
作者：
Case, Natasha;Xie, Zhihui;Sen, Buer;Styner, Maya;Zou, Minxu;O'Conor, Chris;Horowitz, Mark;Rubin, Janet
骨骼重塑的调节似乎影响了骨髓中多潜能间充质干细胞的分化。由于小鼠骨髓培养受到造血细胞的污染，它们在研究机械输入的直接影响方面存在问题。在这里，我们使用一种改进的技术从成年小鼠中分离骨髓来源的MSC(MdMSC)，产生一个能够分化为成脂和成骨表型的群体，但没有造血细胞。在纯mdMSC群体中，每日一次的菌株方案抑制成脂分化，抑制PPARγ和脂联素的表达。菌株增加了β-连环蛋白，抑制脂肪生成需要这种作用。在成骨条件下，菌株激活了β-连环蛋白信号转导通路，增加了WISP1和COX2的表达。缺乏小窝蛋白-1(一种已知的隔离β-连环蛋白的蛋白质)的小鼠也产生了mdMSC：小窝-1(−/−)mdMSC沿成脂和成骨谱系表现出延迟分化，但保留了涉及β-连环蛋白激活的机械反应。有趣的是，小窝蛋白-1(−/−)骨髓间充质干细胞不表达骨涎蛋白，也不形成矿化结节。综上所述，成年小鼠骨髓间充质干细胞对可溶性因子和机械输入都有反应，β-连环蛋白的机械激活影响表型。因此，这些细胞为研究MSC分化和功能的直接机械调控提供了有用的模型。
Regulation of skeletal remodeling appears to influence the differentiation of multipotent mesenchymal stem cells (MSC) resident in the bone marrow. As murine marrow cultures are contaminated with hematopoietic cells, they are problematic for studying direct effects of mechanical input. Here we use a modified technique to isolate marrow-derived MSC (mdMSC) from adult mice, yielding a population able to differentiate into adipogenic and osteogenic phenotypes that is devoid of hematopoietic cells. In pure mdMSC populations, a daily strain regimen inhibited adipogenic differentiation, suppressing expression of PPARγ and adiponectin. Strain increased β-catenin and inhibition of adipogenesis required this effect. Under osteogenic conditions, strain activated β-catenin signaling and increased expression of WISP1 and COX2. mdMSC were also generated from mice lacking caveolin-1, a protein known to sequester β-catenin: caveolin-1(−/−) mdMSC exhibited retarded differentiation along both adipogenic and osteogenic lineages, but retained mechanical responses that involved β-catenin activation. Interestingly, caveolin-1(−/−) mdMSC failed to express bone sialoprotein and did not form mineralized nodules. In summary, mdMSC from adult mice respond to both soluble factors and mechanical input, with mechanical activation of β-catenin influencing phenotype. As such, these cells offer a useful model for studies of direct mechanical regulation of MSC differentiation and function.
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影响因子：
3.7
作者：
Arnsdorf EJ;Tummala P;Jacobs CR
通讯作者：
Jacobs CR
影响因子：
4.8
作者：
Galbiati, F;Volonte, D;Lisanti, MP
通讯作者：
Lisanti, MP
DOI：
10.1016/s0006-291x(02)00824-0
发表时间：
2002-08-09
影响因子：
3.1
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通讯作者：
Chun, JS
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4.8
作者：
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通讯作者：
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影响因子：
56.9
作者：
Drab, M;Verkade, P;Kurzchalia, TV
通讯作者：
Kurzchalia, TV