Wu Erli, Gu Feihan, Zhuo Qiangqiang, Gao Ziyang, Zhang Yu, Li Jingjing, Yin Xuan, Bao Weimin, Zhou Xianqing, Liang Feng, Yang Shouxiang, Wang Yuanyin, Wang Qingqing, Shao Wei
Key Lab. of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, China.
Department of Periodontology, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China.
Front Immunol. 2025 Apr 30;16:1537046. doi: 10.3389/fimmu.2025.1537046. eCollection 2025.
Gingival fibroblasts (GFs), as a critical component of periodontal tissue, play a vital role in processes such as collagen synthesis, wound healing, and tissue repair, thereby maintaining the structural integrity of periodontal tissues. Interestingly, recent studies have revealed that GFs also contribute to the pathophysiology of periodontitis by promoting inflammatory responses. However, its specific molecular mechanism and clinical relevance are still not fully understood.
To find pro-inflammatory gingival fibroblasts (PIGFs) in periodontitis, a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from normal and periodontitis patients was conducted. Then, the role of this celltype in periodontitis was further explored by using cell communication. By merging bulk transcriptome data and employing multiple machine learning algorithms, potential feature genes with PIGFs were further screened, which were verified by qPCR and immunofluorescence staining. Lastly, a cell function test was used to examine the part these genes play in the pathogenesis of periodontitis.
Through single-cell sequencing analysis, we identified PIGFs which were closely related to the development of periodontitis. Cell communication analysis revealed the specific role of PIGFs in periodontitis. Differential gene analysis, WGCNA, and machine learning algorithms identified two genes (MME and TSPAN11) as potential therapeutic targets for periodontitis. Immune infiltration analysis demonstrated a significant correlation between these genes and the immune response. Functionally, down-regulation of MME and TSPAN11 promoted the proliferation and migration of GFs and significantly inhibited the release of inflammatory cytokines and chemokines.
This study identified a subpopulation of GFs closely associated with the inflammatory response through scRNA-seq analysis. These cells may contribute to the progression of periodontitis by interacting with various immune and non-immune cell types. Notably, MME and TSPAN11 were identified as key genes associated with this specific GFs subpopulation that may drive disease progression by exacerbating the inflammatory response, suggesting their potential as therapeutic targets for periodontitis.
牙龈成纤维细胞（GFs）作为牙周组织的关键组成部分，在胶原蛋白合成、伤口愈合和组织修复等过程中发挥着至关重要的作用，从而维持牙周组织的结构完整性。有趣的是，最近的研究表明，GFs还通过促进炎症反应参与牙周炎的病理生理过程。然而，其具体的分子机制和临床相关性仍未完全明确。
为了在牙周炎中找到促炎性牙龈成纤维细胞（PIGFs），对来自正常人和牙周炎患者的单细胞RNA测序（scRNA-seq）数据进行了全面分析。然后，通过细胞通讯进一步探究这种细胞类型在牙周炎中的作用。通过整合批量转录组数据并采用多种机器学习算法，进一步筛选出与PIGFs相关的潜在特征基因，并通过qPCR和免疫荧光染色进行验证。最后，使用细胞功能测试来检验这些基因在牙周炎发病机制中所起的作用。
通过单细胞测序分析，我们鉴定出了与牙周炎发展密切相关的PIGFs。细胞通讯分析揭示了PIGFs在牙周炎中的具体作用。差异基因分析、加权基因共表达网络分析（WGCNA）和机器学习算法确定了两个基因（MME和TSPAN11）作为牙周炎的潜在治疗靶点。免疫浸润分析表明这些基因与免疫反应之间存在显著相关性。在功能上，MME和TSPAN11的下调促进了GFs的增殖和迁移，并显著抑制了炎性细胞因子和趋化因子的释放。
本研究通过scRNA-seq分析鉴定出了与炎症反应密切相关的GFs亚群。这些细胞可能通过与各种免疫和非免疫细胞类型相互作用，促进牙周炎的进展。值得注意的是，MME和TSPAN11被确定为与这种特定GFs亚群相关的关键基因，它们可能通过加剧炎症反应来驱动疾病进展，提示它们作为牙周炎治疗靶点的潜力。
