Pyroptosis of periodontal ligament stem cells aggravates periodontitis via Piezo1 channel.

Periodontitis is a chronic inflammatory disease that leads to periodontal tissue destruction, but the mechanisms underlying inflammation-induced stem cell dysfunction remain unclear. This study examines the role of Piezo1 in modulating pyroptosis in periodontal ligament stem cells (PDLSCs) during periodontitis. Using a mouse model induced by silk ligatures and in vitro PDLSC stimulation with LPS and nigericin, we found that inflammation activated Piezo1, promoting Ca2+ influx and triggering gasdermin D (GSDMD)-mediated pyroptosis, which impaired PDLSC osteogenic differentiation. Inhibiting Piezo1 via small interfering RNA (siRNA) partially restored PDLSC function, while Piezo1 depletion in Wnt1-positive cells or inhibitor treatment alleviated periodontal tissue destruction. These findings provide mechanistic insights into how inflammatory signals drive periodontal degeneration through Piezo1-mediated pyroptosis and suggest that targeting Piezo1 could be a potential therapeutic strategy for periodontitis.