Pyroptosis of periodontal ligament stem cells aggravates periodontitis via Piezo1 channel

Peng Chen; Duo Liu; Yi-Kun Zhou; Jiu-Hui Jiang; Rui-Li Yang

doi:10.1016/j.isci.2025.112395

Pyroptosis of periodontal ligament stem cells aggravates periodontitis via Piezo1 channel

iScience. 2025 Apr 9;28(5):112395. doi: 10.1016/j.isci.2025.112395. eCollection 2025 May 16.

Authors

Peng Chen^{1

2}, Duo Liu¹, Yi-Kun Zhou¹, Jiu-Hui Jiang¹, Rui-Li Yang¹

Affiliations

¹ Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, China.
² Department of Orthodontics, School of Stomatology Affiliated to Medical College, Zhejiang University, Hangzhou 310005, China.

Abstract

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.

Keywords: Piezo1; bone destruction; periodontitis; pyroptosis.