Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain–containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB1 in the plasma membrane.
Enamel formation is a serial and complex biological process, during which related genes are expressed progressively in a spatiotemporal manner. This process is vulnerable to environmental cues, resulting in developmental defects of enamel (DDE). However, how environmental factors are biologically integrated during enamel formation is still poorly understood. Here, we investigated the mechanism of DDE elicited by a model endocrine-disrupting chemical, bisphenol A (BPA), in mouse incisors. We show that BPA exposure leads to DDE in mouse incisors, as well as excessive proliferation in dental epithelial stem/progenitor cells. Western blotting, chromatin immunoprecipitation sequencing, and immunofluorescence staining revealed that this effect was accompanied by upregulation of a repressive mark, H3K27me3, in the labial cervical loop of mouse incisors. Perturbation of H3K27me3 methyltransferase EZH2 repressed the level of H3K27me3 and partially attenuated the excessive proliferation in dental epithelial stem/progenitor cells and DDE induced by BPA exposure. Overall, our results demonstrate the essential role of repressive histone modification H3K27me3 in DDE elicited by exposure to an endocrine-disrupting chemical.
Previous investigations have shown the potential for fluoride to be protective in an abrasion/erosion laboratory model. The aim of this study was to investigate the effect of high concentrations of fluoride delivered in a varnish on attrition of dentine. Fifteen caries-free, intact lower third molar teeth were sectioned and the enamel removed by a water-cooled diamond disc. Polished dentine surfaces were divided into 8 areas, 4 of which were randomly covered with a high-concentration fluoride varnish for 24 h. The samples were subjected to 5,000 cycles of attrition bathed under artificial saliva. Microhardness testing adjacent to the wear scars showed no statistical difference between the fluoride-treated (71.42 KHN, SD 10.52) and control surfaces (72.66 KHN, SD 9.69). The volume of the wear scar was statistically greater for the fluoride-treated surface at 9.6 µm3 (SD 4.92) and 8.13 µm3 (SD 5.54) for the control areas (p = 0.029). The low pH of the fluoride varnish appears to have increased the amount of wear from attrition in this laboratory study.
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