Comprehensive analysis of transcriptome and pathway interactions in periodontitis

Periodontitis involves complex immune, epithelial, and metabolic disruptions. High-throughput transcriptomic approaches can reveal key regulatory networks underpinning disease progression. 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.