| 描述信息 |
Orthodontic tooth movement (OTM) is complicated by unpredictable rates and risks of root resorption, largely due to an incomplete understanding of the mechanotransduction mechanisms that drive alveolar bone remodeling. This study demonstrates that macrophages, through the Piezo1-ZBP1 axis, act as a pivotal mechano-immune switch converting physical stress into osteoclastogenic signals. In response to mechanical stress, macrophage Piezo1 activation triggers Ca2+ influx and subsequent ZBP1 upregulation, a pathway essential for pro-inflammatory cytokine release and osteoclast formation. Multi-level analyses, including clinical human PDL tissue examination, in vivo functional studies with macrophage-specific Piezo1 and Zbp1 knockout murine models (OTM and fracture), and in vitro transcriptomic and pharmacological screening, confirmed that deletion of this axis significantly decelerated OTM and preserved alveolar bone, while Zbp1 overexpression rescued remodeling defects in Piezo1-deficient mice. Crucially, virtual screening identified JNJ-10311795 as a ZBP1 modulator; its administration bidirectionally controlled bone remodeling by slowing OTM and accelerating fracture healing. These findings establish the macrophage Piezo1-ZBP1 axis as a novel therapeutic target, offering a promising strategy for precisely regulating orthodontic movement and enhancing bone repair. |
