Objective To analyze the relationship between periodontal ligament fibroblasts(PDLCs) and ferroptosis-related genes during orthodontic tooth movement using bioinformatics methods.

Methods The transcriptome data of loaded and unloaded periodontal ligament tissue samples and human PDLCs samples were obtained from the GEO database.The key genes related to ferroptosis were screened out through differential gene analysis, GSEA enrichment analysis, intersection analysis with the ferroptosis database, PCA analysis and protein-protein interaction network analysis.The expression of key genes in the loaded and unloaded group were verified using ELISA detection, Western blotting detection and in vitro cell experiments, and their effects on osteoclast generation were explored.Normal distribution data were analyzed by ANOVA, and non-parametric data were analyzed by Wilcoxon signed rank sum test.P value < 0.05 was considered statistically significant.

Results A total of 193 differentially expressed genes were obtained through differential gene analysis, among which 38 were differentially expressed genes related to ferroptosis.The PCA plot showed that there were significant differences in the gene expression patterns between loaded and unloaded group.The protein-protein interaction network diagram was used to screen out key genes such as TFRC.The expression changes of the key gene TFRC before and after orthodontic force application in clinical orthodontic treatment were explored by ELISA.After orthodontic force application, the expression abundance of TFRC in gingival crevicular fluid was significantly upregulated(P < 0.05).In vitro cell experiments showed that under force application, the expression level of TFRC increased over time(P < 0.01).After Fre-1 intervention, the expression level of TFRC was significantly downregulated(P < 0.01), and compared with the control group, the force application group could induce more osteoclasts (P < 0.01).After Fre-1 intervention, the number of induced osteoclasts reducted(P < 0.05).

Conclusions TFRC may promote orthodontic tooth movement by enhancing ferroptosis and osteoclastogenesis, which provides a new insigh and potential target for understanding the mechanisms of orthodontic treatment and optimizing therapeutic strategies.