2024 Volume 38 Issue 2 Pages 80-87
Mechanical forces transmitted to the nucleus that affect nuclear organization, such as nuclear shape and intranuclear DNA distribution, are crucial regulators of key transcriptional activities directing the differentiation of mesenchymal stem cells (MSCs). Several studies have reported that the actin cytoskeleton plays an important role in force transmission to the nucleus, thereby defining nuclear organization. However, the effects of structural changes in the actin cytoskeleton on nuclear organization during osteogenic differentiation remain unclear. Here, we investigated the relationship between the perinuclear actin cytoskeleton and nuclear organization at each stage of osteogenic differentiation of MSCs, based on fluorescence images. The results demonstrated that actin fibers on top of the nucleus transiently developed in the early stage of osteogenic differentiation, which was correlated with a decrease in nuclear height. In addition, we revealed that the development of the actin fibers on top of the nucleus contributed to DNA condensation with histone modification (H3k9me3) in the nuclear peripheral area. These findings suggest that, from MSCs to the early stage of osteogenic differentiation, the compressive forces exerted on the nucleus by the actin cytoskeleton induce a decrease in nuclear height and promote DNA condensation in the nuclear peripheral area.
