Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT(2B) receptor and the ERK1/2 signalling pathway.
Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT(2B) receptor and the ERK1/2 signalling pathway.
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DOI：
10.1016/j.bbrc.2013.10.141
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发表时间：
2013-11
影响因子：
3.1
通讯作者：
Xianxian Li;Yuan-yuan Ma;Xiangnan Wu;Zhichao Hao;Jian Yin;Jie-Fei Shen;Xiaoyu Li;Ping Zhang
中科院分区：
文献类型：
--
作者：
Xianxian Li;Yuan-yuan Ma;Xiangnan Wu;Zhichao Hao;Jian Yin;Jie-Fei Shen;Xiaoyu Li;Ping Zhang
白介素 6 (IL-6) 是破骨细胞骨吸收的有效刺激剂。骨细胞分泌的IL-6在骨代谢中起重要作用。最近有报道称血清素（5-HT）可以调节骨代谢。本研究的目的是评估血清素对骨细胞 IL-6 表达的影响。检查了 5-HT 受体的需求以及细胞外信号调节激酶 1/2 (ERK1/2) 在血清素诱导的 IL-6 合成中的作用。在本研究中，采用实时PCR和ELISA分析血清素刺激的MLO-Y4细胞中IL-6基因和蛋白的表达。通过蛋白质印迹法测定 ERK1/2 通路激活。我们发现，在培养的 MLO-Y4 细胞中，5-羟色胺显着激活 ERK1/2 通路并诱导 IL-6 mRNA 表达和蛋白质合成。然而，通过用 5-HT2B 受体拮抗剂 RS127445 或 ERK1/2 抑制剂 PD98059 预处理 MLO-Y4 细胞，这些效应被消除。我们的结果表明，5-羟色胺刺激骨细胞分泌 IL-6，并且这种作用与 5-HT2B 受体和 ERK1/2 通路的激活有关。这些发现表明血清素通过介导炎症细胞因子来调节骨重塑，从而支持了血清素在骨代谢中的作用。
Interleukin-6 (IL-6) is a potent stimulator of osteoclastic bone resorption. Osteocyte secretion of IL-6 plays an important role in bone metabolism. Serotonin (5-HT) has recently been reported to regulate bone metabolism. The aim of this study was to evaluate the effect of serotonin on osteocyte expression of IL-6. The requirement for the 5-HT receptor(s) and the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) in serotonin-induced IL-6 synthesis were examined. In this study, real-time PCR and ELISA were used to analyse IL-6 gene and protein expression in serotonin-stimulated MLO-Y4 cells. ERK1/2 pathway activation was determined by Western blot. We found that serotonin significantly activated the ERK1/2 pathway and induced IL-6 mRNA expression and protein synthesis in cultured MLO-Y4 cells. However, these effects were abolished by pre-treatment of MLO-Y4 cells with a 5-HT2Breceptor antagonist, RS127445 or the ERK1/2 inhibitor, PD98059. Our results indicate that serotonin stimulates osteocyte secretion of IL-6 and that this effect is associated with activation of 5-HT2Breceptor and the ERK1/2 pathway. These findings provide support for a role of serotonin in bone metabolism by indicating serotonin regulates bone remodelling by mediating an inflammatory cytokine.