The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR China.
Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2389-2401. doi: 10.1016/j.bbamcr.2017.09.015. Epub 2017 Sep 28.
The mechanism by which cell shape regulates the function of the cell is one of the most important biological issues, but it remains unclear. Here, we investigated the effect of the regulation of cell shape on proliferation by using a micropatterning approach to confine MC3T3-E1 cells into specific shapes. Our results show that the proliferation rate for rectangle-, triangle-, square- and circle-shaped osteoblasts increased sequentially and was related to the nuclear shape index (NSI) but not the cell shape index (CSI). Interestingly, intracellular calcium transients also displayed different patterns, with the number of Ca peaks increasing with the NSI in shaped cells. Further causal investigation revealed that the gene expression levels of the inositol 1,4,5-triphosphate receptor 1 (IP3R1) and sarco/endoplasmic reticulum Ca-ATPase 2 (SERCA2), two major calcium cycling proteins in the endoplasmic reticulum (ER), were increased with an increase in NSI as a result of nuclear volume changes. Moreover, the down-regulation of IP3R1 and/or SERCA2 using shRNAs in circle-shaped or control osteoblasts resulted in changes in intracellular calcium transient patterns and cell proliferation rates towards that of smaller-NSI-shaped cells. Our results indicate that changes in cell shape changed nuclear morphology and then the gene expression of IP3R1 and SERCA2, which produced different intracellular calcium transient patterns. The patterns of intracellular calcium transients then determined the proliferation rate of the shaped osteoblasts.
细胞形状如何调节细胞功能是一个非常重要的生物学问题，但目前仍不清楚。在这里，我们通过微图案化方法将 MC3T3-E1 细胞限制在特定形状，研究了细胞形状对增殖的调节作用。结果表明，长方形、三角形、正方形和圆形成骨细胞的增殖率依次增加，与核形状指数（NSI）有关，但与细胞形状指数（CSI）无关。有趣的是，细胞内钙瞬变也显示出不同的模式，形状细胞中钙峰数量随着 NSI 的增加而增加。进一步的因果关系研究表明，内质网（ER）中两种主要的钙循环蛋白肌醇 1,4,5-三磷酸受体 1（IP3R1）和肌浆/内质网 Ca-ATP 酶 2（SERCA2）的基因表达水平随着 NSI 的增加而增加，这是由于核体积变化导致的。此外，使用 shRNA 在圆形或对照成骨细胞中下调 IP3R1 和/或 SERCA2，导致细胞内钙瞬变模式和细胞增殖率发生变化，向 NSI 较小的形状细胞变化。我们的结果表明，细胞形状的变化改变了核形态，进而改变了 IP3R1 和 SERCA2 的基因表达，产生了不同的细胞内钙瞬变模式。细胞内钙瞬变模式决定了形状成骨细胞的增殖率。
