Potential Roles of Long Non-coding RNAs in the Pathogenesis of Periodontitis: Inflammation Response, Immune Infiltration, Collagen Fibers Synthesis, and Bone Remodeling

Abstract

Background: It is evident that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of periodontitis. However, the detailed functional mechanisms remain unknown. Objective: This study aimed to elucidate the pathogenic mechanisms of lncRNAs in periodontitis by investigating their regulation of protein-coding gene expression. Method: Human Gingival Fibroblasts-1 (HGF-1) were stimulated with 5 μg/mL of Lipopolysaccharide (LPS) for 24 hours to construct the periodontitis cell model. qRTPCR and western blot analyses were carried out to determine mRNA and protein levels of genes induced by LPS or involved in the inflammatory response. Cytokine levels and inflammatory proteins were assayed using ELISA. Transcriptome sequencing and analysis were conducted to reveal the expression signatures of lncRNAs. DESeq2 (v1.4.5) was used to analyze differentially expressed genes. Gene function enrichment was carried out using Phyper. AnimalTFDB v3.0 was used to analyze transcription factors involved in the pathogenesis of periodontitis. Prot\ein domains and families of the target proteins were identified based on the Pfam protein family database. Results: In LPS-treated HGF-1 cells, we detected the secretion of TNF-α and IL-1β, along with the production of MDA and ROS, indicating that LPS significantly triggered inflammatory responses and oxidative stress in HGF-1 cells. A total of 15,295 lncRNAs were detected in both the control (ConT) and LPS-treated groups. We selected 10 significantly differentially co-expressed lncRNA-coding genes (MIR222HG, SNHG15, SNHG12, URS00005F6AA3, URS00009C153E, URS0000D57D7F, URS00019A4688, URS00019AF240, URS00019C6526, and URS0001A00B79) as potential biomarkers for diagnosing the progression of periodontitis. An interaction network consisting of 2 lncRNA- encoding genes (MIR222HG and SNHG15) and protein-encoding genes (CBX5, NUPR1, CHAC1, and MAB21L3) may be involved in the pathogenesis of periodontitis. The ceRNA network analysis revealed the differentially expressed lncRNAs to be involved in inflammatory response, immune infiltration, collagen fiber synthesis, and bone remodeling in LPS-induced periodontitis. Conclusion: This study has identified pivotal molecules implicated in the pathogenesis of periodontitis, including those involved in inflammation regulation, collagen fiber synthesis, and bone remodeling. Our findings may contribute to explaining how lncRNAs participate in the pathological process of periodontitis.