Epithelial-specific deletion of FAM20A leads to short root defects.

Short Root Defects defined by a reduced ratio of root to crown, may culminate in root resorption and subsequent tooth loss, in spite of the absence of apparent symptoms. Such defects present considerable impediments to orthodontic treatment and restoration. Recent identification of Fam20a, an emergent pseudokinase, has been associated with enamel development and tooth eruption, yet its definitive role in root formation and eruption remains ambiguous. In this research, we initially ascertained that the targeted knockout of Fam20a within the epithelium led to truncated tooth roots, irregular breaks in the epithelial root sheath initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42 in murine models. This was concomitant with the participation of the associated epithelial root sheath developmental pathways BMP2, Gli1, and Nfic. Furthermore, we observed that Fam20a predominantly affects the intraosseous eruption phase of tooth emergence. During this phase, the osteoclast peak around the mandibular first molar in cKO mice is delayed, leading to a slower formation of the eruption pathway, ultimately resulting in delayed tooth eruption in mice. The findings of this study enrich the extant knowledge regarding the role of Fam20a, suggesting its potential regulatory function in tooth root development through the WNT/ß-catenin/Cdc42 pathway.

Role of ferroptosis-related genes in periodontitis based on integrated bioinformatics analysis.

BACKGROUND: Cell survival or death is one of the key scientific issues of inflammatory response. To regulate cell death during the occurrence and development of periodontitis, various forms of programmed cell death, such as pyroptosis, ferroptosis, necroptosis, and apoptosis, have been proposed. It has been found that ferroptosis characterized by iron-dependent lipid peroxidation is involved in cancer, degenerative brain diseases and inflammatory diseases. Furthermore, NCOA4 is considered one of ferroptosis-related genes (FRGs) contributing to butyrate-induced cell death in the periodontitis. This research aims to analyze the expression of FRGs in periodontitis tissues and to explore the relationship between ferroptosis and periodontitis. METHOD: Genes associated with periodontitis were retrieved from two Gene Expression Omnibus datasets. Then, we normalized microarray data and removed the batch effect using the R software. We used R to convert the mRNA expression data and collected the expression of FRGs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), transcription factor (TF) and protein-protein interaction (PPI) network analyses were used. In addition, we constructed a receiver operating characteristic curve and obtained relative mRNA expression verified by quantitative reverse-transcription polymerase chain reaction (PCR). RESULTS: Eight and 10 FRGs related to periodontitis were upregulated and downregulated, respectively. GO analysis showed that FRGs were enriched in the regulation of glutathione biosynthetic, glutamate homeostasis, and endoplasmic reticulum-nucleus signaling pathway. The top TFs included CEBPB, JUND, ATF2. Based on the PPI network analysis, FRGs were mainly linked to the negative regulation of IRE1-mediated unfolded protein response, regulation of type IIa hypersensitivity, and regulation of apoptotic cell clearance. The expression levels of NCOA4, SLC1A5 and HSPB1 using PCR were significantly different between normal gingival samples and periodontitis samples. Furthermore, the diagnostic value of FRGs for periodontitis were "Good". CONCLUSIONS: We found significant associations between FRGs and periodontitis. The present study not only provides a new possible pathomechanism for the occurrence of periodontitis but also offers a new direction for the diagnosis and treatment of periodontitis.