The Critical Role of Piezo1/CaMKII/β-Catenin Axis in Promoting Osteogenic Differentiation of ADSCs by Pressure Stimulation

The motor system organs respond to mechanical stimuli, and compressive stimulation promotes osteogenesis by enhancing the differentiation and mineralization of mesenchymal stem cells (MSCs) both in laboratory settings and in living organisms. Piezo1, a crucial ion channel, enables cells to detect external mechanical stimuli and mediates various signaling pathways that regulate osteogenesis. However, the function of Piezo1 in the osteogenic differentiation of MSCs triggered by compressive stimulation is still not well understood. To investigate this, we developed an in vitro compressive stress model using a uniaxial compression device. Our findings indicate that compressive stress not only enhances osteogenic differentiation in adipose-derived stem cells (ADSCs) but also significantly increases Piezo1 expression. Mechanistically, compressive stress activates the Piezo1 channel, which, through CA²⁺ as a second messenger, mediates the phosphorylation of CaMKII and directly influences the transcriptional activity of β-catenin. Additionally, a significant influx of CA²⁺ facilitates the nuclear translocation of β-catenin, further promoting osteogenic differentiation. In summary, the activation of Piezo1 leads to the synergistic promotion of osteogenic differentiation via CaMKII and the Wnt/β-catenin pathway under stress stimulation. These findings underscore the importance of the Piezo1/CaMKII/β-catenin interaction in the osteogenic differentiation of ADSCs.