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Shared Cell Death and Immune Pathways Link Periodontitis and Rheumatoid Arthritis

  • Haokun He 1, †,   
  • Shuaifei Pan 1, 2, †,   
  • Ling Chen 1,   
  • Siwen Xiao 1,   
  • Shuguang Cheng 1,   
  • Lian Huang 1,   
  • Qing Zhang 1, 3,   
  • Janak L. Pathak 1, *

Received: 17 Jul 2025 | Revised: 08 Aug 2025 | Accepted: 08 Sep 2025 | Published: 15 Sep 2025

Abstract

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases with striking clinical and pathological similarities. While periodontitis damages periodontal tissues and is linked to systemic conditions like cardiovascular disease and diabetes, RA is an autoimmune disorder causing joint inflammation, pain, and deformity. Both diseases involve dysregulated bone remodeling, inflammatory mediators, and cell death pathways, such as pyroptosis, necroptosis, and ferroptosis, yet their shared molecular mechanisms remain unclear. Using bioinformatics approaches, we analyzed GEO datasets from affected tissues and peripheral blood of patients with periodontitis and RA. Differential gene expression (DEGs), functional enrichment, and co-expression network analyses identified IKZF1, NLRP3, and TREM2 as upregulated cell death-related genes in both diseases. Single-cell RNA-Seq further revealed elevated IL7R and BTN3A2 expression in peripheral blood, implicating leukocyte migration and B-cell receptor signaling. Our findings highlight common DEGs tied to cell death and immune dysfunction in periodontitis and RA. Investigating these shared genes may uncover novel mechanistic links between the two diseases, offering potential therapeutic targets.

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DOI
10.53941/rmd.2025.100012
Issue
Volume 2, Issue 3
How to Cite
He, H.; Pan, S.; Chen, L.; Xiao, S.; Cheng, S.; Huang, L.; Zhang, Q.; Pathak, J. L. Shared Cell Death and Immune Pathways Link Periodontitis and Rheumatoid Arthritis. Regenerative Medicine and Dentistry 2025, 2 (3), 12. https://doi.org/10.53941/rmd.2025.100012.
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