Compliant Substratum Changes Osteocyte Functions: The Role of ITGB3/FAK/β-Catenin Signaling Matters.

Bone shows the potential to adapt its architecture to environmental rigidity via the bone remodeling process, which is governed by osteocytes. Once the remodeling process is disrupted, the mechanics of the bone architecture is impaired, and bone disease proceeds. During the process of pathogenesis, how the osteocytes start the process of sensing and transducing a weakened extracellular mechanical signal into a biochemical signal remains elusive. In the current study, using polydimethylsiloxane (PDMS) substrates with varied mechanical stiffnesses, we first showed that the osteocytes can sense the mechanical change and respond by showing different cell spreading areas and cytoskeleton distributions. Osteocytes sense ECM mechanics via integrin αvβ3, which interacts with focal adhesion kinase (FAK) to promote the transduction of extracellular mechanical stimuli into intracellular biochemical signals. FAK triggers cytoplasmic β-catenin signaling and the resultant nuclear translocation. This signaling results in changes in the gap junction and mineralization activity of the osteocytes. This study establishes the correlation between microenvironmental mechanics and osteocyte function by characterizing the interaction between integrin αvβ3/FAK signaling and β-catenin signaling, thus providing a deep understanding of mechanosensing and mechanotransduction in osteocytes and bone pathogenesis.