Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.
Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.
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循环压缩应力调节大鼠成骨细胞凋亡：PI3K/Akt 和 JNK MAPK 信号通路的参与
DOI：
10.1371/journal.pone.0165845
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Song F;Wang Y;Jiang D;Wang T;Zhang Y;Ma H;Kang Y
生理性机械刺激抑制成骨细胞凋亡并诱导细胞外基质合成已被广泛接受，然而，应力过载对成骨细胞的影响尚未得到充分说明。本研究采用一种新型的液滴法对成骨细胞单层施加机械应力，观察周期性压应力对成骨细胞凋亡的影响。观察成骨细胞在不同程度的机械应力作用下的凋亡情况，以及丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3激酶（PI 3 K）/Akt信号通路的激活情况。在机械刺激前，用特异性抑制剂处理成骨细胞，观察到细胞凋亡。使用蛋白质印迹法测定Bax/Bcl-2/caspase-3信号传导的蛋白水平，使用或不使用PI 3 K/Akt抑制剂和c-jun N-末端激酶（JNK）MAPK磷酸化。结果表明，机械刺激可诱导成骨细胞凋亡，并呈剂量依赖性，同时MAPKs和PI 3 K/Akt信号通路显著激活。PI 3 K/Akt的激活保护细胞免于凋亡，而JNK MAPK通过调节Bax/Bcl-2/caspase-3的激活而增加细胞凋亡。总之，PI 3 K/Akt和JNK MAPK信号通路在成骨细胞凋亡中发挥相反的作用，导致小幅度应力抑制凋亡和大幅度应力增加凋亡。
It is widely accepted that physiological mechanical stimulation suppresses apoptosis and induces synthesis of extracellular matrix by osteoblasts; however, the effect of stress overloading on osteoblasts has not been fully illustrated. In the present study, we investigated the effect of cyclic compressive stress on rat osteoblasts apoptosis, using a novel liquid drop method to generate mechanical stress on osteoblast monolayers. After treatment with different levels of mechanical stress, apoptosis of osteoblasts and activations of mitogen-activated protein kinases (MAPKs) and PI3-kinase (PI3K)/Akt signaling pathways were investigated. Osteoblasts apoptosis was observed after treated with specific inhibitors prior to mechanical stimulation. Protein levels of Bax/Bcl-2/caspase-3 signaling were determined using western blot with or without inhibitors of PI3K/Akt and phosphorylation of c-jun N-terminal kinase (JNK) MAPK. Results showed that mechanical stimulation led to osteoblasts apoptosis in a dose-dependent manner and a remarkable activation of MAPKs and PI3K/Akt signaling pathways. Activation of PI3K/Akt protected against apoptosis, whereas JNK MAPK increased apoptosis via regulation of Bax/Bcl-2/caspase-3 activation. In summary, the PI3K/Akt and JNK MAPK signaling pathways played opposing roles in osteoblasts apoptosis, resulting in inhibition of apoptosis upon small-magnitude stress and increased apoptosis upon large-magnitude stress.