The potential role of spectrin network in the mechanotransduction of MLO-Y4 osteocytes.
The potential role of spectrin network in the mechanotransduction of MLO-Y4 osteocytes.
复制标题
血影蛋白网络在 MLO-Y4 骨细胞力转导中的潜在作用
DOI：
10.1038/srep40940
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发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Fan YB
中科院分区：
文献类型：
--
作者：
Wu XT;Sun LW;Yang X;Ding D;Han D;Fan YB
血影蛋白首次被鉴定为红细胞膜骨架的主要成分。自从在多个非红系细胞中被发现以来，它因提供了复杂的力学性质和细胞膜下的信号接口而受到越来越多的关注。最近的基因组学研究表明，血影蛋白与骨骼疾病高度相关。然而，在骨细胞中，作为骨骼中重要的机械传感器，幽灵蛋白的作用还知之甚少。本研究探讨了血影蛋白在MLO-Y4骨细胞力学转导中的作用。免疫荧光染色显示，光谱蛋白被精心组织成一个贯穿细胞质的多孔网络，并与F-肌动蛋白连接成细胞膜下的致密层。AFM结果表明，血影蛋白在维持骨细胞的整体弹性，尤其是细胞皮质硬度方面起着关键作用。血影蛋白网络的破坏导致骨细胞明显软化，导致钙离子内流、NO分泌和细胞间连接显著增加，并诱导eNOS从膜向胞浆移位。这些结果表明，血影蛋白网络是骨细胞参与机械转导过程的一种全局结构支持，使其成为骨疾病的潜在治疗靶点。
The spectrin is first identified as the main component of erythrocyte membrane skeleton. It is getting growing attention since being found in multiple nonerythroid cells, providing complex mechanical properties and signal interface under the cell membrane. Recent genomics studies have revealed that the spectrin is highly relevant to bone disorders. However, in osteocytes, the important mechanosensors in bone, the role of spectrin is poorly understood. In this research, the role of spectrin in the mechanotransduction of MLO-Y4 osteocytes was studied. Immunofluorescence staining showed that, the spectrins were elaborately organized as a porous network throughout the cytoplasm, and linked with F-actin into a dense layer underlying the cell membrane. AFM results indicate that, the spectrin is pivotal for maintaining the overall elasticity of osteocytes, especially for the cell cortex stiffiness. Disruption of the spectrin network caused obvious softening of osteocytes, and resulted in a significant increase of Ca2+influx, NO secretion, cell-cell connections and also induced a translocation of eNOS from membrane to cytoplasm. These results indicate that the spectrin network is a global structural support for osteocytes involving in the mechanotransduction process, making it a potential therapeutic target for bone disorders.