Biological significance and regulatory networks of mRNAs, lncRNAs, and circRNAs in human periodontal ligament tissues induced by orthodontic tooth movement.

Abstract

Objective: Orthodontic tooth movement (OTM) is a dynamic biological process driven by mechanically induced tissue remodeling. The transcriptional regulators, particularly the noncoding RNAs in human tissues remains limited. This study employs RNA sequencing and bioinformatics to analyze the transcriptomic profile at day 7 of OTM, and to identify potential regulatory factors associated with mechanical stimulus.

Methods: RNA sequencing was performed on human periodontal ligament tissues obtained from extracted first premolars of OTM and non-OTM (control) patients (n = 3 per group) after seven days of orthodontic force application. Differentially expressed mRNAs, lncRNAs, and circRNAs were identified, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Competing endogenous RNAs (ceRNA) networks and a mechanical stimulus-related circRNA-miRNA-mRNA network were constructed using bioinformatic approaches. qRT-PCR was applied for validation in an independent set of samples (n = 5 per group).

Results: Compared with control group, a total of 337 mRNAs, 687 lncRNAs, and 377 circRNAs were significantly up-regulated in human periodontal ligament tissues of the OTM group. Conversely, 341 mRNAs, 1253 lncRNAs, and 109 circRNAs exhibited down-regulated expression during OTM. GO and KEGG analyses highlighted key biological functions and signaling pathways involved in bone modeling, with significant enrichment of inflammatory and immune-effector pathways. A predicted lncRNA/circRNA-miRNA-mRNA network active during OTM was constructed, and the circELP3-hsa-miR-629-3p/hsa-miR-29b-2-5p-TLR7/ITGAM axis was identified as potential regulatory pathway related to mechanical stimulus. This finding was subsequently validated by qRT-PCR.

Conclusion: mRNAs, lncRNAs, and circRNAs in human periodontal tissues are differentially expressed at day 7 of OTM, and form a complex ceRNA network. The circELP3-hsa-miR-629-3p/hsa-miR-29b-2-5p-TLR7/ITGAM axis might be involved in mechanical stimulus of OTM at day 7. These findings provide insights and molecular clues that could inform future strategies for modulating bone remodeling in periodontal tissues during orthodontic treatment.