Chen Peng, Liu Duo, Zhou Yi-Kun, Jiang Jiu-Hui, Yang Rui-Li
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.
Department of Orthodontics, School of Stomatology Affiliated to Medical College, Zhejiang University, Hangzhou 310005, China.
iScience. 2025 Apr 9;28(5):112395. doi: 10.1016/j.isci.2025.112395. eCollection 2025 May 16.
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 PDLSC stimulation with LPS and nigericin, we found that inflammation activated Piezo1, promoting Ca 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.
牙周炎是一种导致牙周组织破坏的慢性炎症性疾病，但炎症诱导干细胞功能障碍的潜在机制仍不清楚。本研究探讨了Piezo1在牙周炎期间调节牙周膜干细胞（PDLSCs）焦亡中的作用。使用丝线结扎诱导的小鼠模型以及用脂多糖（LPS）和尼日利亚菌素刺激PDLSCs，我们发现炎症激活了Piezo1，促进钙离子内流并触发gasdermin D（GSDMD）介导的焦亡，这损害了PDLSCs的成骨分化。通过小干扰RNA（siRNA）抑制Piezo1可部分恢复PDLSCs功能，而Wnt1阳性细胞中Piezo1缺失或抑制剂处理可减轻牙周组织破坏。这些发现为炎症信号如何通过Piezo1介导的焦亡驱动牙周退变提供了机制性见解，并表明靶向Piezo1可能是牙周炎的一种潜在治疗策略。
