ROLE OF MECHANICAL STRAIN AND ESTROGEN IN MODULATING OSTEOGENIC DIFFERENTIATION OF MESENCHYMAL STEM CELLS (MSCS) FROM NORMAL AND OVARIECTOMIZED RATS

ROLE OF MECHANICAL STRAIN AND ESTROGEN IN MODULATING OSTEOGENIC DIFFERENTIATION OF MESENCHYMAL STEM CELLS (MSCS) FROM NORMAL AND OVARIECTOMIZED RATS
复制标题

机械应变和雌激素在调节正常和卵巢切除大鼠间充质干细胞(MSC)成骨分化中的作用

DOI:
10.1170/225
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发表时间:
2013-01-01
影响因子:
1.6
通讯作者:
Tang, M.
Tang, M.
中科院分区:
生物学4区
文献类型:
--
作者:
Li, L.;Yao, X. L.;Tang, M.

文献摘要

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骨对载荷的适应性取决于骨重建的过程。这种适应性机制在绝经后骨质疏松症中受到限制。骨髓间充质干细胞(mesenchymal stem cells,MSCs)的分化是骨重建和再生的关键。众所周知,机械负荷影响MSC分化的命运。本研究旨在通过观察假手术和去卵巢大鼠骨髓间充质干细胞的反应,探讨其在骨质疏松状态下可能的抑制机制。将骨髓间充质干细胞暴露于雌激素和机械应变(2%,1Hz,6 h/天),持续3天。检测MSCs的成骨分化和β-连环蛋白表达。暴露于雌激素和机械应变单独增强表达Runx 2(Cbf α 1),I型胶原(ColI)和活化的β-连环蛋白在MSC从假手术和OVX大鼠。从假手术和OVX大鼠骨髓间充质干细胞刺激与机械应变和雌激素有更高的表达成骨基因和激活β-连环蛋白比这些细胞暴露于雌激素和机械应变单独。与假手术大鼠相比,在无刺激和有刺激的情况下,骨质疏松症MSCs的成骨基因和蛋白表达均较低。累积起来,我们的研究结果表明,机械应变和雌激素在体外增强成骨潜力和激活β-连环蛋白在骨髓间充质干细胞从假手术和OVX大鼠。雌激素增强骨髓间充质干细胞中应变诱导的成骨潜能和β-连环蛋白的活性
Bone's adaptability to loading depends upon the process of bone remodeling. This adaptive mechanism is restricted in postmenopausal osteoporosis. Differentiation of mesenchymal stem cells (MSCs) is crucial to bone remodeling and regeneration. It is well accepted that mechanical loading influences the fate of MSC differentiation. The aim of this study was to explore the possible restricted mechanism in osteoporotic condition, through investigating response of MSCs from both sham-operated and ovariectomized rats. MSCs were exposed to estrogen and mechanical strain (2%, 1Hz, 6h/day) for 3 days. Osteogenic differentiation and beta-catenin protein in MSCs were examined. Exposure to estrogen and mechanical strain alone enhanced expression of Runx2 (Cbf alpha 1), type I collagen (ColI) and activated beta-catenin protein in MSCs from both sham-operated and OVX rats. MSCs from both sham-operated and OVX rats stimulated with both mechanical strain and estrogen had higher expression of osteogenic genes and activated beta-catenin protein than these cells exposed to estrogen and mechanical strain alone. Osteoporotic MSCs had lower expression of osteogenic genes and protein in the absence and presence of stimulation than did MSCs from sham-operated rats. Cumulatively, our results indicate that mechanical strain and estrogen in vitro enhance osteogenic potential and activation of beta-catenin in MSCs from both sham-operated and OVX rats. Estrogen augments strain-induced osteogenic potential and activity of beta-catenin in MSCs.