Piezo‐type mechanosensitive cation channel 1 in bone biomechanics and its multidimensional distribution characteristics in skeletal tissue

Abstract Mechanical stress coordinates bone growth, resorption, and formation through a complex and multidimensional biological mechanism. During mechanical loading, the piezo‐type mechanosensitive cation channel 1 (PIEZO1)—the primary mechanotransducer in bone—mediates the mechanochemical conversion of biomechanical signals into cellular biochemical cascades that modulate skeletal adaptation. This article comprehensively reviewed PIEZO1's role in bone biomechanics and systematically analyzed its multidimensional distribution across biomechanical stress fields, including four‐dimensional (4D) spatiotemporal localization ( x, y, z, t ) and cell‐type‐specific patterning. The analysis of the relationship of mechanical bone stimulation with PIEZO1 expression and distribution revealed the following: (1) PIEZO1 expression correlated positively with the capacity for mechanically driven bone modeling, (2) PIEZO1 exhibited rapid transcriptional responses to mechanical loading, and (3) distinct biomechanical stress fields conferred unique spatiotemporal and cell‐type‐specific distribution patterns on PIEZO1. Based on these insights, this review proposes the following: (1) targeting PIEZO1 and its downstream pathways could represent a novel therapeutic strategy for osteoporosis (OP), and (2) PIEZO1 could serve as a real‐time quantitative biomarker for the skeletal mechanoresponsive status. This study offers a timely theoretical advance and charts an innovative methodological direction in bone biomechanics and mechanobiology.