New Study: The First Construction of a Transcriptomic Regulatory Network for Orthodontic Tooth Movement by the Third Affiliated Hospital of Sun Yat-sen University

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

DentalGoodNews｜A transcriptomic study published in the European Journal of Orthodontics (2026, Vol. 48, Issue 4, cjag053) on July 7, 2026, reported that the Department of Stomatology at the Third Affiliated Hospital of Sun Yat-sen University constructed, for the first time, a comprehensive transcriptomic regulatory network of mRNA, lncRNA, and circRNA in human periodontal ligament tissue during orthodontic tooth movement (OTM), and identified a circELP3-hsa-miR-629-3p/hsa-miR-29b-2-5p-TLR7/ITGAM regulatory axis potentially involved in immune-inflammatory responses.

The research team recruited 16 healthy subjects aged 18-25 years who required extraction of the first premolars due to mild crowding or rotation and received labial fixed orthodontic treatment. They were randomly divided into an orthodontic force group and a control group: in the force group, brackets were bonded across the full arch with 0.014-inch nickel-titanium wires ligated, and teeth were extracted after 7 days of continuous force application (4 premolars per patient were pooled into one sample); in the control group, teeth were extracted before force application. Among these, 3 samples per group were used for RNA sequencing, and another 5 independent samples per group were used for qRT-PCR validation.

Sequencing results showed that in the periodontal ligament tissue of the force group, a total of 337 mRNAs were upregulated and 341 downregulated, 687 lncRNAs upregulated and 1253 downregulated, and 377 circRNAs upregulated and 109 downregulated (|log2 fold change|>1.0, P<0.05). Gene Ontology (GO) and KEGG pathway analyses revealed that upregulated genes were significantly enriched in cytokine-mediated signaling pathways, immune responses, and neutrophil extracellular trap (NET) formation-related pathways; downregulated genes were concentrated in extracellular matrix structure, PI3K-Akt signaling pathway, and circadian rhythm-related pathways.

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

Through protein-protein interaction network and module analysis, the research team identified that upregulated genes TLR7 (Toll-like receptor 7) and ITGAM (integrin alpha-M, i.e., CD11b) participate in NET formation. Further ceRNA network analysis and qRT-PCR validation suggested that 4 upregulated circRNAs (including circELP3, derived from the ELP3 gene locus with its circular structure confirmed by Sanger sequencing) may competitively bind hsa-miR-629-3p and hsa-miR-29b-2-5p, thereby relieving the inhibition on TLR7 and ITGAM, thus forming the aforementioned regulatory axis.

The research team also noted that the ceRNA network relationships are bioinformatic predictions and have not yet been validated by direct molecular interaction experiments such as luciferase reporter assays. The sample size of this study is relatively small (RNA sequencing n=3/group, qRT-PCR validation n=5/group), with samples collected only at a single time point (day 7 after force application) and from a single institution. Therefore, the relevant conclusions require further validation through multicenter, multi-time-point, and higher cell-type resolution studies.

This study was funded by the National Natural Science Foundation of China, the Guangzhou Science and Technology Plan Project, and the Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University, and was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (Approval No. RG2024-098-01). The sequencing data have been deposited in the NCBI Gene Expression Omnibus (GEO) database.