Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka, Suma-ku, Kobe, Japan.
Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka, Suma-ku, Kobe, Japan; Department of Rehabilitation, Kobe City Medical Center General Hospital, Chuo-ku, Kobe, Japan.
J Biomech. 2021 Dec 2;129:110774. doi: 10.1016/j.jbiomech.2021.110774. Epub 2021 Sep 29.
Chondrocytes as mechano-sensitive cells can sense and respond to mechanical stress throughout life. In chondrocytes, changes of structure and morphology in the cytoskeleton have been potentially involved in various mechano-transductions such as stretch-activated ion channels, integrins, and intracellular organelles. However, the mechanism of cytoskeleton rearrangement in response to mechanical loading and unloading remains unclear. In this study, we exposed chondrocytes to a physiological range of cyclic tensile strain as mechanical loading or to simulated microgravity by 3D-clinostat that produces an unloading environment. Based on microarray profiling, we focused on Fat1 that implicated in the formation and rearrangement of actin fibers. Next, we examined the relationship between the distribution of Fat1 proteins and actin fibers after cyclic tensile strain and microgravity. As a result, Fat1 proteins did not colocalize with actin stress fibers after cyclic tensile strain, but accumulated near the cell membrane and colocalized with cortical actin fibers after microgravity. Our findings indicate that Fat1 may mediate the rearrangement of cortical actin fibers induced by mechanical unloading.
软骨细胞作为机械敏感细胞,可以在整个生命周期中感知和响应机械应激。在软骨细胞中,细胞骨架的结构和形态变化可能参与了各种机械转导,如拉伸激活的离子通道、整合素和细胞内细胞器。然而,细胞骨架对机械加载和卸载的重排机制尚不清楚。在这项研究中,我们通过 3D 回转仪使软骨细胞暴露于生理范围内的周期性拉伸应变(即机械加载)或模拟微重力(产生卸载环境)。基于微阵列分析,我们专注于 Fat1,它与肌动蛋白纤维的形成和重排有关。接下来,我们研究了周期性拉伸应变和微重力后 Fat1 蛋白与肌动蛋白纤维的分布关系。结果表明,周期性拉伸应变后 Fat1 蛋白与肌动蛋白应力纤维没有共定位,但在微重力后聚集在细胞膜附近并与皮质肌动蛋白纤维共定位。我们的研究结果表明,Fat1 可能介导了机械卸载诱导的皮质肌动蛋白纤维的重排。