Contribution of endoplasmic reticulum stress response to the mechanosensitivity alteration in osteocytes under simulated microgravity
Contribution of endoplasmic reticulum stress response to the mechanosensitivity alteration in osteocytes under simulated microgravity
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模拟微重力下内质网应激反应对骨细胞机械敏感性变化的贡献
DOI：
10.1016/j.actaastro.2021.11.037
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发表时间：
2021-12
影响因子：
3.5
通讯作者：
Sun Lian-Wen
中科院分区：
文献类型：
--
作者：
Liu Li-Jin;Li Shuang;Wu Xin-Tong;Yang Xiao;Sun Lian-Wen
微重力导致骨质疏松症的分子和细胞机制尚不清楚。我们先前的研究表明，这可能是由于骨细胞的机械敏感性降低所致。有研究表明，内质网应激(ERS)可以影响细胞的机械反应。本研究探讨了内质网在模拟微重力(SMG)下骨细胞机械敏感性改变中的作用。MLO-Y4细胞(骨样细胞系)在SMG下培养48h，然后在流室中施加15dyn/cm2的流体剪应力1h，并加入ERS拮抗剂褪黑素(MT，200nmoL/L)来抑制ERS。免疫荧光法检测内质网形态，Western印迹和qPCR检测ERS标志物(GRP78)，qPCR检测未折叠蛋白途径(UPR)相关因子(IRE1、XBP1S、PERK、ATF4、ATF6)和凋亡相关因子(CHOP)，ELISA法测定机械敏感因子(NO、PGE2和ATP)。结果表明，SMG时内质网增大，内质网/核面积比明显增大，形态不规则，GRP78和UPR相关因子表达显著增加，FSS诱导的NO、PGE2和ATP含量降低。此外，MT还可对抗SMG诱导的上述效应。ERs可能在微重力下骨细胞的力学敏感性改变中起重要作用。
The molecular and cellular mechanism of microgravity-induced osteoporosis is unclear. Our previous study showed that it may be due to the decreased mechanosensitivity of osteocytes. Some research indicated that endoplasmic reticulum stress (ERS) could affect the mechanical response of cells. This study investigated the role of ERS in the altered mechanosensitivity of osteocytes under simulated microgravity (SMG). MLO-Y4 cells (osteocyte-like cell line) were cultured under SMG for 48 h and then applied 15 dyn/cm2fluid shear stress (FSS) in the flow chamber for 1 h. In addition, melatonin (MT, 200 nmol/L), an ERS antagonist, was added to inhibit ERS. The morphology of endoplasmic reticulum was examined by immunofluorescence, ERS marker (GRP78) by Western blot and qPCR, unfolded protein pathway (UPR) related factors (IRE1, XBP1s, PERK, ATF4, ATF6) and apoptosis-related factor (CHOP) by qPCR and the mechanical sensitive factors (NO, PGE2 and ATP) by ELISA were determined. The results showed that under SMG, the endoplasmic reticulum enlarged as the endoplasmic reticulum/nucleus area ratio increased significantly and the morphology was irregular; the expression of GRP78 and UPR related factors increased significantly; NO, PGE2 and ATP induced by FSS decreased. Furthermore, MT could counter above SMG-induced effect. ERS may play an important role in the mechanosensitivity alteration in osteocytes under microgravity.
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使用新型旋转细胞培养装置研究剪切应力和模拟微重力对骨细胞的影响
影响因子：
3.5
作者：
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DOI：
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发表时间：
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影响因子：
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DOI：
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发表时间：
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影响因子：
3.1
作者：
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通讯作者：
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