Cytoskeletal control of nuclear morphology and stiffness are required for OPN-induced bone-marrow-derived mesenchymal stem cell migration
Cytoskeletal control of nuclear morphology and stiffness are required for OPN-induced bone-marrow-derived mesenchymal stem cell migration
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OPN 诱导的骨髓间充质干细胞迁移需要细胞骨架对核形态和硬度的控制
DOI：
10.1139/bcb-2018-0263
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发表时间：
2019
影响因子：
2.9
通讯作者：
Song Guanbin
中科院分区：
文献类型：
--
作者：
Liu Lingling;Luo Qing;Sun Jinghui;Song Guanbin
在细胞迁移过程中，细胞核的运动必须与影响细胞迁移效率的细胞骨架动力学相协调。我们之前的研究表明，骨桥蛋白（OPN）显著促进骨髓间充质干细胞（BMSCs）的迁移。然而，在opn促进的骨髓间充质干细胞迁移过程中，调控细胞骨架核力学的机制尚不清楚。在这项研究中，我们研究了肌动蛋白细胞骨架如何影响骨髓间充质干细胞的核力学。我们评估了opn处理的骨髓间充质干细胞中受到肌动蛋白细胞骨架破坏或聚合的细胞核的形态和力学。我们发现细胞松弛素D （Cyto D）对肌动蛋白组织的破坏导致核投射面积和核硬度的减少。用茉莉素内酯（JASP）稳定肌动蛋白组装导致核投射面积和核刚度增加。SUN1 （Sad-1/ unc - 841）是LINC（核骨架和细胞骨架的连接物）复合体的一个组成部分，参与细胞核和细胞骨架之间的连接。我们发现，RNAi耗尽SUN1降低了核刚度，opn促进了BMSC迁移。因此，f -肌动蛋白细胞骨架在决定细胞核的形态和力学特性方面起着重要作用。我们认为，通过SUN1蛋白的细胞骨架-核互联性在opn促进的BMSC迁移中起重要作用。
During cell migration, the movement of the nucleus must be coordinated with the cytoskeletal dynamics that influence the efficiency of cell migration. Our previous study demonstrated that osteopontin (OPN) significantly promotes the migration of bone-marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism that regulates nuclear mechanics of the cytoskeleton during OPN-promoted BMSC migration remains unclear. In this study, we investigated how the actin cytoskeleton influences nuclear mechanics in BMSCs. We assessed the morphology and mechanics of the nuclei in the OPN-treated BMSCs subjected to disruption or polymerization of the actin cytoskeleton. We found that disruption of actin organization by cytochalasin D (Cyto D) resulted in a decrease in the nuclear projected area and nuclear stiffness. Stabilizing the actin assembly with jasplakinolide (JASP) resulted in an increase in the nuclear projected area and nuclear stiffness. SUN1 (Sad-1/UNC-84 1) is a component of the LINC (linker of nucleoskeleton and cytoskeleton) complex involved in the connections between the nucleus and the cytoskeleton. We found that SUN1 depletion by RNAi decreased the nuclear stiffness and OPN-promoted BMSC migration. Thus, the F-actin cytoskeleton plays an important role in determining the morphology and mechanical properties of the nucleus. We suggest that the cytoskeletal–nuclear interconnectivity through SUN1 proteins plays an important role in OPN-promoted BMSC migration.