Laboratory of Experimental Immunology & Cancer, Faculty of Dentistry, University of Chile, Santiago, Chile.
Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile.
Int J Oral Sci. 2024 May 27;16(1):43. doi: 10.1038/s41368-024-00306-y.
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，但它与进行性牙周炎的关系尚未被探索。为了研究铁死亡在牙周炎进展中的作用和意义，我们评估了 16 名被诊断为牙周炎的患者。通过每周的临床评估来监测疾病在 12 周内的进展，并进行牙龈沟液（GCF）采集以进行进一步分析。临床指标、蛋白质组学数据、计算方法和生物信息学工具相结合，以鉴定与牙周炎进展相关的蛋白质谱，并探讨其与铁死亡的潜在联系。随后的 Western blot 分析验证了关键发现。最后，我们分析了一个牙龈组织的单细胞 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。研究发现，牙周炎的进展速度比传统观念认为的要快。来自进展期和非进展期牙周部位的 GCF 样本显示出定量和定性上截然不同的蛋白质组学特征。此外，还揭示了进行性牙周炎期间特定的生物学过程和分子功能，以及一组与牙周炎临床进展状态密切相关的核心蛋白，包括 SNCA、CA1、HBB、SLC4A1 和 ANK1。此外，我们发现了一些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），揭示了在牙周炎的临床进展过程中，这种特定类型的细胞死亡的共同发生。此外，将定量蛋白质组学数据与 scRNA-seq 分析相结合，提示成纤维细胞对铁死亡的敏感性。我们的分析首次在牙周炎患者中揭示了与铁死亡相关的蛋白和过程，为研究进行性牙周病的分子机制提供了新的见解。这些发现可能为新的诊断和治疗策略提供依据。
