Kang Lixun, Shi Binglu, Shen Siyu, Ma Kai, Jing Yuanxu, An Qi, Dai Yan
Department of Periodontal Implantology, Stomatology Center, Heilongjiang Provincial Hospital, 82 Zhongshan Road, Xiangfang District, Harbin City, 150036, Heilongjiang Province, China.
Department of Material Science and Engineering, City University of Hong Kong, 83 Tat Chee Road, Kowloon Tong, Hong Kong, 999077, China.
Inflammation. 2025 May 30. doi: 10.1007/s10753-025-02316-2.
Periodontitis is a long-lasting inflammatory condition that significantly affects people's quality of life. This research focused on examining the function and underlying mechanisms of X-box binding protein 1 (XBP1) in the pathogenesis of periodontitis. In vitro and in vivo models of periodontitis were established using lipopolysaccharide (LPS). The viability and apoptosis of periodontal ligament stem cells (PDLSCs) were assessed using the Cell Counting Kit-8 and flow cytometry assays, respectively. Reverse transcription-quantitative PCR, western blot, and enzyme-linked immunosorbent assays were employed to measure the levels of inflammatory factors and mediators associated with T helper 17 (Th17)/regulatory T cell (Treg) balance, pyroptosis, and the interleukin-17 (IL-17) pathway. Histological and immunohistochemical analyses were conducted to evaluate tissue damage and bone resorption markers. The IL-17 pathway was activated with SR0987 to explore the interactions between XBP1 and IL-17 signaling. XBP1 knockdown reduced apoptosis, pyroptosis, and inflammation, as indicated by lower levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18) and pyroptosis-related proteins (ASC, GSDMD-N, NLRP3). XBP1 knockdown alleviated tissue damage, inflammatory cell infiltration, and bone destruction in rat models of periodontitis. XBP1 knockdown notably restored the Th17/Treg imbalance by suppressing Th17 differentiation and promoting Treg differentiation. Mechanistically, XBP1 knockdown inhibited the IL-17 signaling pathway, and IL-17Activator SR0987 significantly reversed the beneficial effects of XBP1 knockdown on periodontitis. XBP1 knockdown alleviated periodontitis by inhibiting the IL-17 signaling pathway, implying that XBP1 could serve as a promising therapeutic target for managing periodontal conditions.
牙周炎是一种长期的炎症性疾病，严重影响人们的生活质量。本研究聚焦于检测X盒结合蛋白1（XBP1）在牙周炎发病机制中的作用及潜在机制。使用脂多糖（LPS）建立了牙周炎的体外和体内模型。分别使用细胞计数试剂盒-8和流式细胞术检测牙周膜干细胞（PDLSCs）的活力和凋亡情况。采用逆转录定量PCR、蛋白质免疫印迹法和酶联免疫吸附测定法来检测与辅助性T细胞17（Th17）/调节性T细胞（Treg）平衡、细胞焦亡和白细胞介素-17（IL-17）途径相关的炎症因子和介质水平。进行组织学和免疫组织化学分析以评估组织损伤和骨吸收标志物。用SR0987激活IL-17途径以探究XBP1与IL-17信号之间的相互作用。XBP1基因敲低减少了细胞凋亡、细胞焦亡和炎症，表现为促炎细胞因子（TNF-α、IL-6、IL-1β、IL-18）和细胞焦亡相关蛋白（ASC、GSDMD-N、NLRP3）水平降低。XBP1基因敲低减轻了牙周炎大鼠模型中的组织损伤、炎性细胞浸润和骨破坏。XBP1基因敲低通过抑制Th17分化和促进Treg分化显著恢复了Th17/Treg失衡。机制上，XBP1基因敲低抑制了IL-17信号通路，而IL-17激活剂SR0987显著逆转了XBP1基因敲低对牙周炎的有益作用。XBP1基因敲低通过抑制IL-17信号通路减轻了牙周炎，这意味着XBP1可能是治疗牙周疾病的一个有前景的治疗靶点。
