| Piezo1, a mechanosensitive ion channel protein, extensively modulates diverse cellular physiological and pathological processes. Osteoblasts, as pivotal cells for bone formation, are critical for skeletal integrity; their dysfunction directly contributes to diminished bone strength and the development of skeletal disorders like osteoporosis. By transducing mechanical stimuli into intracellular calcium signaling and influencing mitochondrial function, Piezo1 regulates processes such as endoplasmic reticulum (ER) stress, autophagy, iron metabolism, and inflammatory responses, ultimately governing programmed cell death (PCD) in osteoblasts. Recent research highlights the crucial, yet complexly interrelated roles of various osteoblast PCD modalities – including apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis – in bone formation and homeostasis maintenance. Piezo1 emerges as a key regulator across several of these PCD pathways. It modulates osteoblast fate by impacting calcium signaling, influencing the Bcl-2 family proteins, the PI3K/AKT pathway, the AMPK-ULK1 axis, iron homeostasis, and NLRP3 inflammasome activation. Consequently, elucidating the precise mechanisms by which Piezo1 regulates osteoblast PCD holds significant promise for identifying novel therapeutic targets and strategies for bone-related diseases. This review comprehensively summarizes the regulatory role of Piezo1 in osteoblast PCD and explores its potential crosstalk mechanisms, thereby providing a theoretical foundation for future investigations. |