Mechanical force induces pyroptosis in periodontal ligament (PDL) progenitor cells, which regulates orthodontic tooth movement (OTM) and alveolar bone remodeling. Pyroptosis, an inflammatory caspase-dependent programmed cell death, is involved in tissue homeostasis and inflammatory responses. This study shows that mechanical force increases pyroptosis-related markers in PDL progenitor cells during OTM and alveolar bone remodeling. Blocking or enhancing pyroptosis levels suppresses or promotes OTM and alveolar bone remodeling, respectively. Caspase-1 is essential for force-induced pyroptosis in PDL progenitor cells, as demonstrated by experiments using Caspase-1 knockout mice. Mechanical force also induces pyroptosis in human ex-vivo PDL progenitor cells and in vitro compressive force-loaded PDL progenitor cells, influencing osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 (TRPV4) signaling is involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. TRPV4 regulates Ca²+ influx, which contributes to reactive oxygen species (ROS) elevation and mitochondrial damage. These findings suggest that Caspase-1-dependent pyroptosis is a novel mechanism contributing to OTM and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.Mechanical force induces pyroptosis in periodontal ligament (PDL) progenitor cells, which regulates orthodontic tooth movement (OTM) and alveolar bone remodeling. Pyroptosis, an inflammatory caspase-dependent programmed cell death, is involved in tissue homeostasis and inflammatory responses. This study shows that mechanical force increases pyroptosis-related markers in PDL progenitor cells during OTM and alveolar bone remodeling. Blocking or enhancing pyroptosis levels suppresses or promotes OTM and alveolar bone remodeling, respectively. Caspase-1 is essential for force-induced pyroptosis in PDL progenitor cells, as demonstrated by experiments using Caspase-1 knockout mice. Mechanical force also induces pyroptosis in human ex-vivo PDL progenitor cells and in vitro compressive force-loaded PDL progenitor cells, influencing osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 (TRPV4) signaling is involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. TRPV4 regulates Ca²+ influx, which contributes to reactive oxygen species (ROS) elevation and mitochondrial damage. These findings suggest that Caspase-1-dependent pyroptosis is a novel mechanism contributing to OTM and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.