(A–D) Human femoral neck cortical bone samples obtained from hip arthroplasty procedures were cleared of soft tissues. Subsequently, they were incubated overnight, followed by DEX and Yoda1 treatment for 6 hours (n = 3). Four experimental groups were established: Control (untreated), Yoda1 alone (10 μM), DEX alone (1 μM), and DEX+Yoda1 (combination of 1 μM DEX and 10 μM Yoda1). (E) WB analysis of Piezo1 and β-actin protein levels in MLO-Y4 cells following overnight treatment with DEX and subsequent 24-hour exposure to Yoda1. (F and G) WB analysis of Akt and ERK phosphorylation in response to DEX treatment and subsequent 2 hours of Yoda1 administration. (H) MLO-Y4 cells were incubated with DEX (0.1 and 1 μM) for 24 hours. Subsequently, all groups were treated with Yoda1 (1 μM) to monitor changes in Ca²⁺ influx (n = 3). (I) Yoda1 (10 μM) to monitor changes in Ca²⁺ influx (n = 3). (J) Impact of KN-93, a CaMKII selective inhibitor, on Akt phosphorylation in MLO-Y4 cells treated with DEX, preincubated with KN-93 for 2 hours, and then exposed to Yoda1 for 1 hour. (K and L) Morphological changes in F-actin structure in MLO-Y4 cells subjected to DEX and Yoda1 for 72 hours were visualized using rhodamine-phalloidin (see Supplemental Methods) and Hoechst 33342 staining. Images were acquired using an In Cell Analyzer 6000 at ×40 magnification (scale bars: 50 μm). (L) Actin cross-linking points were quantified (n = 8). Results are presented as the mean ± SD. Statistical significance was evaluated using a 1-way ANOVA followed by a Tukey-Kramer post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001 for Control vs. DEX (0.1 μM) + Yoda1; †P < 0.05, ††P < 0.01, †††P < 0.001 for Control vs. DEX (1 μM) + Yoda1.