SIRT1 and osteoporosis: Our study was designed to (1) determine whether mechanical unloading alters Piezo1 expression and impairs mitochondrial function in BMSCs, (2) investigate if pharmacological activation of Piezo1 by Yoda1 can rescue osteogenic differentiation and mitochondrial biogenesis in mechanically unloaded BMSCs, (3) elucidate whether the AMPK/SIRT1/PGC-1α signaling axis is both necessary and sufficient for mediating the effects of Piezo1 activation, (4) establish whether SIRT1-dependent signaling mediates the protective effects of Yoda1 in a murine model of disuse osteoporosis.