NMDA enhances stretching-induced differentiation of osteobalsts through the ERK1/2 signaling pathway
NMDA enhances stretching-induced differentiation of osteobalsts through the ERK1/2 signaling pathway
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DOI：
10.1016/j.bone.2008.05.018
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发表时间：
2008-09-01
期刊：
影响因子：
4.1
通讯作者：
Liu, Jian-min
中科院分区：
文献类型：
--
作者：
Li, Jie-li;Cui, Bin;Liu, Jian-min
兴奋性神经递质N-甲基-D-天冬氨酸（NMDA）的激活和拉伸均增加成骨细胞中的Ca 2+内流。我们推测NMDA会增强成骨细胞对拉伸的反应。本研究的目的是探讨在神经递质NMDA的存在下，机械负荷油成骨细胞的分化阶段和丝裂原活化蛋白激酶（MAPK）信号通路的影响。预处理与0.5 mM NMDA显着增强拉伸幅度依赖性增加成骨市场。NMDA受体拮抗剂MK 801可阻断上述反应。为了进一步研究这种反应的机制，成骨细胞在不存在NMDA的情况下拉伸5，15或60分钟。周期性牵张诱导细胞外信号调节激酶ERK 1/2磷酸化的快速增加，在15分钟达到峰值，但在p38和JNK通路信号转导中没有观察到变化。NMDA可增强牵张刺激的ERK 1/2磷酸化。ERK 1/2抑制剂U 0126可阻断成骨细胞增殖。总之，目前的研究表明，在成骨细胞中，机械刺激和NMDA之间存在协同效应。ERK 1/2信号通路可能是成骨细胞在NMDA存在下对拉伸反应增加的共同途径。(C)2008年爱思唯尔公司All rights reserved.
Activation of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) and stretching both increase Ca2+ influx in osteoblastic cells. We Postulated that NMDA would enhance the osteoblastic cell's response to stretching. The goal of this study was to investigate, in the presence of the neurotransmitter NMDA, the effect mechanical loading oil osteoblast's stage of differentiation and the mitogen-activated protein kinase (MAPK) signaling pathway associated with it. Rat primary osteoblastic cells were subjected to cyclic, equibiaxial stretch for 48 h in the presence or absence of NMDA. Pretreatment with 0.5 mM NMDA significantly enhanced the stretching magnitude-dependent increase in osteogenesis markets. MK801, an antagonist of NMDA receptors, abolished those responses. To further study the mechanism of this response, osteoblastic cells were stretched for 5, 15, or 60 min in the absence of NMDA. Cyclic stretch induced a rapid increase in extracellular signal-regulated kinase ERK1/2 phosphorylation with the peak at 15 min, but no changes were noted in p38 and JNK pathway signaling. NMDA Could enhance ERK1/2 phosphorylation stimulated by stretching. U0126, an inhibitor of ERK1/2, blocked the increase ill osteogenesis markets. In conclusion, the current study demonstrates that there is a synergistic effect between mechanical stimulation and NMDA in osteoblasts. ERK1/2 signaling may be the common pathway in the increased response to stretching in the presence of NMDA in osteoblastic cells. (C) 2008 Elsevier Inc. All rights reserved.