114027
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
整合多组学与机器学习揭示过氧化物酶 4 是牙周炎中线粒体功能障碍和 B 细胞分化的关键枢纽
Authors Tu C, Luo Y, Jiang T, Yang Z, Yang B, Zhang K, Zhang J, Hu C, Zhou L, Qiu T, Xia H, Xi Z, Hu R, Sun M
Received 11 August 2025
Accepted for publication 13 December 2025
Published 24 December 2025 Volume 2025:17 Pages 661—680
DOI https://doi.org/10.2147/CCIDE.S560013
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Christopher E. Okunseri
Congyi Tu,1,* Yaxian Luo,2,* Tianle Jiang,1,* Zhan Yang,1,3,* Bingqian Yang,2 Kechen Zhang,1 Jingyu Zhang,2 Chaoming Hu,1 Lijun Zhou,3 Tao Qiu,2 Haorong Xia,1 Ziyu Xi,1 Rongdang Hu,1 Mouyuan Sun2
1Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Dentistry, Yongkang First People’s Hospital of Wenzhou Medical University, Jinhua, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Mouyuan Sun, Email sunmouyuan777@zju.edu.cn Rongdang Hu, Email hurongdang@wmu.edu.cn
Aim: Periodontitis, a highly prevalent chronic inflammatory disease, progressively destroys tooth-supporting tissues, ultimately leading to tooth loss, and significantly increases systemic risks such as cardiovascular disease and diabetic complications. Current mechanical therapies effectively control clinical symptoms but fail to eradicate pathogenic microenvironments or restore periodontal homeostasis. Mitochondrial dysfunction is a critical driver of periodontitis progression; however, the regulatory mechanisms of mitochondria-related genes remain poorly defined.
Materials and Methods: This study integrated bulk transcriptome sequencing (bulk RNA-seq) and single-cell RNA-seq (scRNA-seq) analyses to identify mitochondrial dysfunction-associated immune cell alterations in periodontitis. Key mitochondria-related genes inducing disease progression were pinpointed through non-negative matrix factorization (NMF) and weighted gene coexpression network analysis (WGCNA). By integrating ten machine learning algorithms with experimental validation using real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence, peroxiredoxin 4 (PRDX4) was identified as the most crucial hub gene governing mitochondrial homeostasis in periodontitis.
Results: Patient stratification based on PRDX4 expression revealed upregulated B cell-related pathways. Pseudotime analysis demonstrated a synchronized upregulation of PRDX4 and B cell signature genes during late-stage disease progression. scRNA-seq and immunofluorescence confirmed PRDX4 upregulation in B cells, particularly in plasma cells and memory B cells, and indicated its involvement in B cell differentiation. Experiments in a mouse model further validated the conserved functional role of PRDX4 in regulating B cells during periodontitis. Finally, we screened traditional Chinese medicinal compounds and identified aloe as a potential PRDX4 inhibitor.
Conclusion: These findings establish PRDX4 as a key regulatory node linking mitochondrial dysfunction to periodontitis pathogenesis, providing insights into mitochondria-related genes and potential therapeutic strategies.
Keywords: periodontitis, mitochondria, B cell, multi-omics, PRDX4
1Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Dentistry, Yongkang First People’s Hospital of Wenzhou Medical University, Jinhua, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Mouyuan Sun, Email sunmouyuan777@zju.edu.cn Rongdang Hu, Email hurongdang@wmu.edu.cn
Aim: Periodontitis, a highly prevalent chronic inflammatory disease, progressively destroys tooth-supporting tissues, ultimately leading to tooth loss, and significantly increases systemic risks such as cardiovascular disease and diabetic complications. Current mechanical therapies effectively control clinical symptoms but fail to eradicate pathogenic microenvironments or restore periodontal homeostasis. Mitochondrial dysfunction is a critical driver of periodontitis progression; however, the regulatory mechanisms of mitochondria-related genes remain poorly defined.
Materials and Methods: This study integrated bulk transcriptome sequencing (bulk RNA-seq) and single-cell RNA-seq (scRNA-seq) analyses to identify mitochondrial dysfunction-associated immune cell alterations in periodontitis. Key mitochondria-related genes inducing disease progression were pinpointed through non-negative matrix factorization (NMF) and weighted gene coexpression network analysis (WGCNA). By integrating ten machine learning algorithms with experimental validation using real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence, peroxiredoxin 4 (PRDX4) was identified as the most crucial hub gene governing mitochondrial homeostasis in periodontitis.
Results: Patient stratification based on PRDX4 expression revealed upregulated B cell-related pathways. Pseudotime analysis demonstrated a synchronized upregulation of PRDX4 and B cell signature genes during late-stage disease progression. scRNA-seq and immunofluorescence confirmed PRDX4 upregulation in B cells, particularly in plasma cells and memory B cells, and indicated its involvement in B cell differentiation. Experiments in a mouse model further validated the conserved functional role of PRDX4 in regulating B cells during periodontitis. Finally, we screened traditional Chinese medicinal compounds and identified aloe as a potential PRDX4 inhibitor.
Conclusion: These findings establish PRDX4 as a key regulatory node linking mitochondrial dysfunction to periodontitis pathogenesis, providing insights into mitochondria-related genes and potential therapeutic strategies.
Keywords: periodontitis, mitochondria, B cell, multi-omics, PRDX4