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. 2025 Oct 20:33:e20250396.
doi: 10.1590/1678-7757-2025-0396. eCollection 2025.

Comprehensive analysis of transcriptome and pathway interactions in periodontitis

Bruno César de Vasconcelos Gurgel  1 , Nathalia Vilela  2 , Kaio Henrique Soares  3 , Luiz Eduardo Rodrigues Juliasse  1   4 , Ikramuddin Aukhil  5 , Poliana Mendes Duarte  6
Affiliations

Comprehensive analysis of transcriptome and pathway interactions in periodontitis

Bruno César de Vasconcelos Gurgel et al. J Appl Oral Sci. .

Abstract

Objective: To investigate the transcriptomic profile and dysregulated molecular pathways associated with severe periodontitis.

Methodology: Gingival tissues from patients with severe periodontitis (n=11) and periodontally healthy controls (n=11) were compared using RNA sequencing in this cross-sectional study. Differentially expressed genes (DEGs) were identified and analyzed using Ingenuity Pathway Analysis (IPA). Selected DEGs were validated at the protein level via immunohistochemistry (IHC).

Results: A total of 909 DEGs were upregulated and 742 were downregulated in periodontitis versus healthy tissues. Highly upregulated genes included MT-RNR1, MTRNR2L12, pseudogenes, long non-coding RNAs, and immunoglobulins. Downregulated genes included ADGRG7, C6orf15, members of enzyme families, keratin family members, loricrin (LOR), and immune modulators, such as CD207 (Langerin) and DEFB4A. IPA predicted the Wnt/β-catenin pathway as the most upregulated and the IL-17 signaling pathway as the most suppressed canonical pathway in periodontitis. The expression of the level of protein of LOR, Wnt10b, JUN, and FOS was confirmed by IHC.

Conclusion: Dysregulation in key canonical signaling pathways and the altered expression of genes critical to cell chemotaxis, innate immunity, and epithelial barrier integrity seem to play a pivotal role in the pathogenesis of periodontitis.

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Conflict of interest statement

Conflict of interest: The authors have no conflicts of interest to declare.

Figures

None
Graphical abstract
Figure 1
Figure 1. Volcano plot of differential gene expression between periodontitis and healthy groups. The x-axis represents log2 fold change, and the y-axis shows –log10(p-value). Vertical dashed lines indicate fold change thresholds, and the horizontal dashed line marks the significance cutoff (p<0.05). Red dots indicate genes with p-values < 0.05, upregulated on the right side of the plot and downregulated on the left. Gray dots represent genes that have not significantly changed. Green dots indicate genes meeting the log2 fold change threshold only, and blue dots indicate genes meeting the p-value threshold only.
Figure 2
Figure 2. IPA analysis of the canonical pathways related to the DEGs in tissues with periodontitis compared with tissues with periodontal health. (A) The top ten dysregulated canonical signaling pathways are shown in descending order of statistical significance of −log(p-values). (B) The canonical pathways that were predicted to be modulated in periodontitis, as defined by a −log(p-value) >1.5 and Z-score ≥1 (activated) or ≤−1 (inhibited). (C) The number of upregulated and downregulated DEGs involved in each of the canonical pathways.
Figure 3
Figure 3. The immunohistochemical staining using antibodies against LOR (A-B), Wnt10b (C-D), FOS (E-F), and JUN (G-H), and in representative gingival biopsies from the healthy and periodontitis groups. Bar length = 50 μm, original magnification × 200.
See this image and copyright information in PMC

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