PIEZO1-mediated calcium influx transiently alters nuclear mechanical properties via actin remodeling in chondrocytes.

Abstract

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca²⁺ ion channel, has been shown to be important in sensing mechanical stress, however its signal transduction pathway is not thoroughly understood. In this study, we used primary porcine chondrocytes to determine whether PIEZO1 activation and subsequent Ca²⁺ influx altered nuclear mechanical properties, and whether these effects involved the actin cytoskeleton. We discovered that activating PIEZO1 with Yoda1, a specific small-molecule agonist, induces transient nuclear softening-a previously identified mechanoprotective response. This PIEZO1-mediated nuclear softening is abolished by inhibiting actin cytoskeleton remodeling with Latrunculin A or by removing extracellular Ca²⁺. Notably, PIEZO1-mediated nuclear softening did not lead to significant changes in gene expression or heterochromatin methylation. Our findings demonstrate that actin cytoskeleton remodeling following Ca²⁺ influx facilitates PIEZO1 signal transduction to the nucleus but does not induce lasting gene expression changes.