ヒト間葉系幹細胞の細胞核内粘弾性変化の骨芽細胞分化における役割

抄録

Human mesenchymal stem cells (hMSC) change their lineage specification in response to the mechanical properties of the extracellular matrix. In this signaling process, the mechanical forces are transmitted to the cell nucleus via the actin cytoskeleton. The forces are reported to affect the expression of differentiation-related genes by altering the organization and the dynamics of chromatin, which is a DNA-protein complex, both locally and globally. However, the mechanism has not been elucidated. Quantitative data about the local mechanical properties in the cell nucleus during the hMSC lineage specification are essential for understanding the mechanosensing and mechanotransduction mechanisms in regulation of hMSC differentiation. Here, we quantified the intranuclear local mechanical properties of hMSC during osteogenic differentiation with particle tracking microrheology. At the same time, we also quantified the actin filament architecture and chromatin condensation level. In particular, the intranuclear local loss tangent that is the ratio of loss modulus to storage modulus increased from the beginning to the end of osteoblast differentiation. The changes in the intranuclear local loss tangent will be a result of the changes in chromatin condensation level and may affect the efficiency of force transmission to the nucleus via the actin during osteoblast differentiation. Viscoelastic energy loss at a late stage of the osteoblast differentiation may contribute to ensure intranuclear mechanical stability.