Abstract
Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for in vitro experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-κB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.
Highlights
Dental pulp inflammation, or termed pulpitis, is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps (Hall et al, 2016)
According to the expression profiles of 241 disease samples, using platelet endothelial cell adhesion molecule-1 (PECAM1) as the phenotype, the B-cell receptor and the B-cell migration signaling pathways were found to be enriched on the side showing positive correlation with PECAM1, which was in line with the Gene Set Variation Analysis (GSVA) results (Figures 1D,E)
Our study revealed a novel regulatory work, where a transcription factor MEF2C activates the transcription of PECAM1 and CXCR4, leading to activation of the NF-κB signaling pathway
Summary
Termed pulpitis, is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps (Hall et al, 2016). Occurring without any evidence of bacteria in the pulp chamber (Agnihotry et al, 2019), pulpitis can be a progressive and torturously painful experience attributed to spontaneous or provoked pain, allodynia, hyperalgesia, and inadequate local anesthesia (Galicia et al, 2016). Pulpitis is induced by a response to persistent, severe stimuli which may cause massive apoptosis of dental pulp cells and inflammatory damage, contributing to long-term tissue loss and innate repair impairments (Bei et al, 2017; Ding et al, 2019). Identifying novel molecular regulatory networks implicated in inflammatory responses and in pulpitis progression may be helpful for the management of this disease.
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