Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.

铁死亡与许多慢性炎症性疾病的发病机制有关，但其与进行性牙周炎的关系仍未被探索。为了调查铁死亡在牙周炎进展中的参与和意义，我们评估了 16 名牙周炎诊断患者。通过每周临床评估在十二周内对疾病进展进行临床监测，并收集龈沟液（GCF）以进行进一步分析。结合临床指标、蛋白质组数据、计算机方法和生物信息学工具来识别与牙周炎进展相关的蛋白质谱，并探索它们与铁死亡的潜在联系。随后的蛋白质印迹分析验证了主要发现。最后，分析牙龈组织的单细胞 RNA 测序 (scRNA-seq) 数据集 (GSE164241)，以阐明牙周炎进展过程中的细胞动态。牙周炎的进展速度被认为比传统认为的要快。来自进展和非进展牙周部位的 GCF 样本显示出定量和定性不同的蛋白质组谱。此外，还揭示了进行性牙周炎期间的特定生物过程和分子功能，并且一组枢纽蛋白，包括SNCA、CA1、HBB、SLC4A1和ANK1与牙周炎的临床进展状态密切相关。此外，我们发现了与铁死亡相关的特定蛋白（驱动蛋白或抑制蛋白）（SNCA、FTH1、HSPB1、CD44 和 GCLC），揭示了牙周炎临床进展过程中这种特定类型的受调节细胞死亡的同时发生。 此外，定量蛋白质组数据与 scRNA-seq 分析的整合表明成纤维细胞对铁死亡的易感性。我们的分析首次揭示了牙周患者中与铁死亡相关的蛋白质和过程，这为渐进性牙周病的分子机制提供了新的见解。这些发现可能会带来新的诊断和治疗策略。