Marginal effect of hydrostatic pressure on osteogenic differentiation of mesenchymal stem cells and its mechanism

Hydrostatic pressure (HP) is one of the important mechanical stimuli to maintain the structure and function of bone tissue. Under non-physiological conditions, abnormal increases or decreases in HP can lead to loss of bone tissue function. Although HP has been proven to affect osteogenic differentiation, the rules and mechanisms of its regulatory effect are still unclear. In this study, the HP showed a marginal effect on promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The regulation of osteogenic differentiation by HP is closely related to the Piezo1 ion channel. On the one hand, the activity of mTOR is inhibited by HP through the CaMKK2/AMPKα/mTOR signaling axis, thereby promoting the osteogenic differentiation. On the other hand, the cell morphology is also regulated by HP and tends to be round, which is not conducive to osteogenesis. The two regulatory modes jointly control the ultimate osteogenic differentiation ability of BMSCs in a complex way. This study provides new insights into the mechanism by which HP regulates osteogenic differentiation, suggesting the need to consider the role of signaling cascades and physical changes simultaneously.