ERK1/2 is involved in cyclic compressive force-induced IL-6 secretion in MLO-Y4 cells.
ERK1/2 is involved in cyclic compressive force-induced IL-6 secretion in MLO-Y4 cells.
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DOI：
10.1016/j.bbrc.2010.09.044
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Wenchuan Chen;Yuan-yuan Ma;H. Ye;Yun He;Xiaoyu Li;Jihua Li;Zhimin Zhu;Hang Wang
中科院分区：
文献类型：
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作者：
Wenchuan Chen;Yuan-yuan Ma;H. Ye;Yun He;Xiaoyu Li;Jihua Li;Zhimin Zhu;Hang Wang
我们先前报道了周期性压力（CCF）诱导骨细胞样MLO-Y 4细胞中白细胞介素-6 mRNA的表达。但是对于刺激如何在MLO-Y 4细胞中转化为生化信号知之甚少。本研究旨在探讨CCF对IL-6分泌的影响及细胞外信号调节激酶1/2（ERK 1/2）在此过程中的作用。采用四点弯曲系统，以不同的应变强度（1000、2000和4000μ应变）、频率（0.5、1.0和2.0Hz）和持续时间（10、30、1、3和6 h）对细胞进行CCF处理。ELISA法检测细胞IL-6分泌水平，Western blotting法检测细胞ERK 1/2磷酸化水平。结果表明，CCF可显著上调IL-6蛋白的分泌，并呈强度、频率和持续时间依赖性。ERK 1/2的磷酸化也在所有情况下增加，但不依赖于CCF的幅度，频率或持续时间。此外，ERK 1/2途径的特异性抑制剂PD 098059的抑制减少但不完全消除应激MLO-Y 4细胞的IL-6分泌。这些结果表明，CCF诱导的IL-6分泌发生通过一种机制，涉及ERK 1/2信号通路，并表明，这一事件的调制有助于骨质疏松症的发病机制和应力诱导的病理性骨吸收以及。
We previously reported that cyclic compressive force (CCF) induced interleukin-6 mRNA expression in osteocyte-like MLO-Y4 cells. But little is known about how the stimuli are converted into the biochemical signals in MLO-Y4 cells. The aim of this research was to study the effect of CCF on the IL-6 secretion and the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in this process. The cells were exposed to CCF with different magnitudes (1000, 2000 and 4000μstrain), frequencies (0.5, 1.0 and 2.0Hz) and durations (10min, 30min, 1h, 3h and 6h) by a four-point bending system. The IL-6 secretion and ERK1/2 phosphorylation of the cells were determined by ELISA and Western blotting, respectively. The results showed that IL-6 protein secretion was significantly up-regulated in response to CCF in a magnitude-, frequency- and duration-dependent fashion. The phosphorylation of ERK1/2 also increased in all cases but not depended on the magnitude, frequency or duration of CCF. Furthermore, the inhibition of the ERK1/2 pathway by its specific inhibitor PD098059 decreased but not completely abrogated the IL-6 secretion from stressed MLO-Y4 cells. These findings demonstrate that CCF-induced IL-6 secretion occurs via a mechanism that involves ERK1/2 signaling pathway and suggest that modulation of this event contributes to the pathogenesis of osteoporosis and stress-induced pathological bone resorption as well.