Time-Course Study of Genetic Changes in Periodontal Ligament Regeneration in Tooth Transplantation

This study aimed to comprehensively analyze gene expression in the periodontal ligament (PDL) following reimplantation to elucidate the genes and pathways involved in healing and regeneration after treatment. Using a mouse model for intentional tooth replantation, mRNA was extracted from the PDL at various intervals post-replantation for comparative transcriptome analysis via RNA sequencing (RNA-seq). The analysis covered intervals from 3 days to 8 weeks post-replantation. Results showed significant changes in gene expression patterns, especially on day 28. Hierarchical clustering and principal component analysis further validated these findings. Gene ontology (GO) enrichment analysis revealed an upregulation of olfactory and G protein-coupled receptor signaling pathways at day 28. qRT-PCR validation confirmed the transient expression of olfactory receptor genes, and immunochemical staining further localized this expression to the PDL and adjacent tissue. Additionally, a scratch assay using human PDL fibroblasts indicated a potential role for the olfactory receptor gene in wound healing, suggesting that a transient increase in olfactory receptor gene expression might aid optimal PDL healing. On the other hand, by 14 days post-replantation, there was an increase in inflammatory pathways and a decrease in genes linked to keratinization and epithelial barrier function. These results underscore the importance of the 28-day post-transplant phase as a potential "tipping point" in PDL healing and regeneration. In conclusion, this research provides insights into the gene expression patterns during the PDL's healing and regeneration processes, highlighting the potential role of olfactory receptor genes.