ABSTRACT
OBJECTIVES: The aim of this study was to investigate the molecular mechanism underlying odontoblast damage repair in dentin hypersensitivity (DH) and the role of Yes-associated protein (YAP) in this process. METHODS: The DH model was constructed in Sprague-Dawley (SD) rats, and the in vivo expression of Piezo1, Integrin αvß3, YAP, and dentin sialophosphoprotein (DSPP) was detected by immunohistochemistry. COMSOL Multiphysics software was used to simulate the dentinal tubule fluid flow velocity and corresponding fluid shear stress (FSS) on the odontoblast processes. MDPC-23 cells were cultured in vitro and loaded with a peristaltic pump for 1 hour at FSS values of 0.1, 0.3, 0.5, and 0.7 dyne/cm2. The expression of Piezo1, Integrin αvß3, and YAP was detected by immunofluorescence. Verteporfin (a YAP-specific inhibitor) was utilised to confirm the effect of YAP on the expression of dentineogenesis-related protein under FSS. RESULTS: The level and duration of external mechanical stimuli have an effect on the functional expression of odontoblasts. In DH, the harder the food that is chewed, the faster the flow of the dentinal tubule fluid and the greater the FSS on the odontoblast processes. The expression of Piezo1, Integrin αvß3, and YAP can be promoted when the FSS is less than 0.3 dyne/cm2. After YAP inhibition, the DSPP protein expression level was reduced at 0.3 dyne/cm2 FSS. CONCLUSIONS: These results suggest that appropriate FSS can enhance the expression of odontoblast-related factors in odontoblasts via the Piezo1-Integrin αvß3-YAP mechanotransduction pathway and the YAP appears to play an essential role in the response of odontoblasts to external mechanical stimuli.
Subject(s)
Dentin Sensitivity , Disease Models, Animal , Odontoblasts , Rats, Sprague-Dawley , YAP-Signaling Proteins , Odontoblasts/metabolism , Animals , Rats , Phosphoproteins/metabolism , Integrin alphaVbeta3/metabolism , Stress, Mechanical , Extracellular Matrix Proteins/metabolism , Sialoglycoproteins/metabolism , Ion Channels/metabolism , Immunohistochemistry , Adaptor Proteins, Signal Transducing/metabolism , Verteporfin/pharmacology , Verteporfin/therapeutic use , Male , Membrane ProteinsABSTRACT
OBJECTIVE: The aim of this study was to identify candidate genes and gene sets associated with dental caries by an integrative analysis of transcriptome-wide association study (TWAS) and messenger RNA (mRNA) expression profiling of dental caries. METHODS: A genome-wide association study (GWAS) dataset of dental caries was obtained from the UK Biobank. A TWAS of dental caries was conducted with the FUSION tool using the gene expression reference weights of musculoskeletal, whole blood, and peripheral blood genes. The dental caries-associated genes identified by the TWAS were further subjected to gene ontology (GO) and pathway enrichment analyses to explore dental caries-related gene sets. Finally, the TWAS results of dental caries were compared with genome-wide mRNA expression profiling of dental caries to detect common genes and gene sets. RESULTS: The TWAS identified 165 musculoskeletal genes, 110 whole blood genes, and 228 peripheral blood genes. GO analysis of the genes identified by the TWAS detected 57 GO terms. For pathway enrichment analysis, we detected 12 candidate pathways. After comparing the TWAS-identified genes with the mRNA expression profiling data, we detected 6 common genes. Further comparing the GO results of the TWAS and mRNA expression profiling identified 5 common GO terms. CONCLUSION: We identified a group of dental caries-associated genes and GO terms, providing novel clues for understanding the genetic mechanisms of dental caries.
