Effect of Long Non-coding RNA and DNA Methylation on Gene Expression in Dental Fluorosis

In the process of tooth development, the interaction between genetic information, epigenetic inheritance, and environment jointly affects the teeth formation. At present, the mechanism of dental fluorosis is rarely studied from transcriptomics, and there is no report on epigenetic perspective. In the study, SD rats were randomly divided into dental fluorosis group and control group fed with NaF (150 mg/L) or distilled water for 8 weeks. After 3.5 days of birth, the RNAs or DNA of rat mandibular molars were detected by RNA-seq or MethylTarget, respectively. The results demonstrated that a total of 1723 differentially expressed genes (DEGs) and 2511 differential expression lncRNAs (DE-lncRNAs) were mainly involved in the ion channels, calcium ion transport, and immunomodulatory signaling pathways. ATP2C1 and Nr1d1, which were related to Ca²⁺ transport, cellular calcium homeostasis, endoplasmic reticulum stress and immunity, may be the key genes in the formation of dental fluorosis. Notably, we also found that the immune response plays an important role in the formation of dental fluorosis, and a large amount of DEGs was enriched in immune regulation and NF-κB signaling pathways. Furthermore, the methylation levels of 13 sites were increased in Ago4, Atf3, Atp2c1, Dusp1, Habp4, and Mycl, while methylation levels of 5 CpG sites decreased in Ago4, Atp2c1, Habp4, and Traf6, and conformably, the expression of these genes have been significantly changed. This study comprehensively analyzed the occurrence mechanism of dental fluorosis from transcriptomics and epigenetics, so as to provide theoretical reference for further research.