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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway.
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A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway.

机译:短脉冲机械力通过ERK 1/2途径诱导MC3T3-E1成骨细胞中的基因表达和生长。

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Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4-30g corresponds to physiological levels of 40-300 microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase in expression of growth-related immediate early gene c-fos, a 5-fold increase in egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP-1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dose-dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15-minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126 significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK 1/2-mediated pathway.
机译:生理机械负荷对于维持骨骼完整性和结构至关重要。我们已经计算出了由成骨细胞上的重力应力引起的应变,发现4-30g对应于40-300微应变的生理水平。短期重力加载(15分钟)诱导与生长相关的立即早期基因c-fos表达增加15倍,egr-1增加5倍,自分泌bFGF增加3倍。与生长无关的基因EP-1,TGF-beta和18s不受重力加载的影响。短期生理负荷以剂量依赖的方式诱导细胞外信号调节激酶(ERK 1/2)磷酸化,最大磷酸化在12g的机械负荷水平下达到饱和(p <0.001),而对总ERK无影响。粘着斑激酶(FAK)的磷酸化不受机械力的影响。 g加载未激活P38 MAPK或c-jun N末端激酶(JNK)。另外,重力脉冲导致磷酸化的ERK1 / 2定位于细胞核。这在卸载的单元中没有发生。 MEK1 / 2抑制剂U0126抑制c-fos诱导74%(p <0.001),但不受MEK1或p38 MAPK特异性抑制剂影响。单个15分钟重力脉冲的长期后果是细胞生长增加64%(p <0.001)。 U0126显着抑制了重力诱导的生长50%(p <0.001)。这些研究表明,短期的生理机械应力主要通过ERK 1/2介导的途径诱导MC3T3-E1成骨细胞中立即的早期基因表达和生长。

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