Changes in the Mechanical Interaction Between Actin Cytoskeleton and Nucleus in Osteogenic Differentiation in Human Mesenchymal Stem Cells

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  • 間葉系幹細胞の骨芽細胞分化進行におけるアクチン線維-細胞核の力学作用の変化

Abstract

<p>Mechanotransduction, in which mechanical forces and deformations are converted into biochemical signals to change gene expression, is a critical factor for directing the differentiation of mesenchymal stem cells. Localization change in a mechanotransducer yes-associated protein (YAP) in course of osteogenic differentiation is a key for efficient osteogenic differentiation, however the detailed mechanism remains unclear. In this study, we hypothesized that YAP localization is regulated by the mechanical interaction between actin cytoskeleton and nucleus, and the changes in the mechanical interaction play an important role in progression of osteogenic differentiation. We analyzed the three-dimensional morphologies of the actin cytoskeleton and the nucleus, and YAP localization in course of osteogenic differentiation. From undifferentiated to early stage of the differentiation, thick actin fibers were developed on the top of the nucleus, and nuclear height was decreased. At this stage, YAP was highly localized in the nucleus, which was suppressed by inhibition of actin polymerization on the top of nucleus. At middle stage of the differentiation, thick actin fibers decreased, and nuclear height was higher than the other stages regardless of the density of the actin fibers on top of the nucleus. At these stages, YAP nuclear localization was suppressed. YAP nuclear localization in the early stage of the osteogenic differentiation could be triggered by compressive forces applied from the actin fibers on the top surface of the nucleus.</p>

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