Piezo1 agonist 1-d 2 (Compound 12a) is an agonist for Piezo1 with an EC 50 of 2.21 μM. Piezo1 agonist 1-d 2 activates the Ca 2+ -related ERK signaling pathway, and thus promotes the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Piezo1 agonist 1-d 2 ameliorates disuse osteoporosis in the hindlimb-unloading (HU) rat model.