Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation.

Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation.
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褪黑素对细胞外调节激酶信号通路激活及人成骨细胞系hFOB 1.19增殖的影响

DOI:
10.3390/ijms160510337
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发表时间:
2015-05-07
影响因子:
5.6
通讯作者:
Yuan W
Yuan W
中科院分区:
生物学2区
文献类型:
--
作者:
Xiong XC;Zhu Y;Ge R;Liu LF;Yuan W

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研究表明,褪黑激素可能会影响骨骼代谢。然而,褪黑激素是否能促进成骨细胞增殖存在争议,褪黑激素对成骨细胞增殖的确切分子机制尚不清楚。本研究CCK-8实验结果显示,褪黑素在浓度为1、2.5、5、10、25、50和100µM时,能显著促进人成骨细胞系hFOB 1.19细胞增殖24 h,但各组间无显著差异。Western blot结果显示,10µM褪黑素显著促进ERK1/2磷酸化。此外,我们还检测到c-Raf, MEK1/2, p90RSK和MSK1的磷酸化,并且在10µM褪黑激素的作用下,它们都增加了。U0126(一种破坏ERK1/2下游活化的MEK选择性抑制剂)下调ERK1/2、p90RSK和MSK1的磷酸化。U0126还能减弱褪黑素刺激的成骨细胞的增殖。综上所述,本研究首次发现褪黑素(10 nM-100µM)通过激活c-Raf、MEK1/2、ERK1/2、p90RSK和MSK1,促进人成骨细胞系hFOB 1.19的增殖。
It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed that melatonin significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation at 1, 2.5, 5, 10, 25, 50 and 100 µM concentrations for 24 h, but there were no significant differences among the groups. Western blot demonstrated that 10 µM melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them increased with 10 µM melatonin. U0126 (a selective inhibitor of MEK that disrupts downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2, p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts stimulated by melatonin. In conclusion, this study for the first time indicates that melatonin (10 nM–100 µM) promotes the proliferation of a human osteoblastic cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1.
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