Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^−/− mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

细胞焦亡是一种炎症性半胱天冬酶依赖性程序性细胞死亡，在维持组织稳态和激活炎症反应中发挥着至关重要的作用。正畸牙齿移动（OTM）是一种无菌力诱导的炎症性骨重塑过程，由牙周膜（PDL）祖细胞的激活介导。然而，力是否以及如何诱导 PDL 祖细胞焦亡，从而影响 OTM 和牙槽骨重塑仍不清楚。在本研究中，我们发现机械力诱导大鼠OTM和牙槽骨重塑过程中焦亡相关标志物的表达。阻断或增强焦亡水平可以分别抑制或促进OTM和牙槽骨重塑。使用Caspase-1 ^−/−小鼠，我们进一步证明了PDL祖细胞中力诱导的细胞焦亡的功能作用取决于Caspase-1。此外，机械力还可诱导人体外受力处理的 PDL 祖细胞和体外受压缩力负载的 PDL 祖细胞焦亡，从而影响破骨细胞生成。从机制上讲，瞬时受体电位亚家族 V 成员 4 信号传导参与了 PDL 祖细胞中力诱导的 Caspase-1 依赖性细胞焦亡。总的来说，这项研究提出了一种在机械刺激下调节破骨细胞生成和牙槽骨重塑的新机制，表明了一种通过靶向 Caspase-1 来加速 OTM 的有前景的方法。