Clefting of the lip, with or without palatal involvement (CLP), is associated with a higher incidence of developmental tooth abnormalities, including hypodontia and supernumerary teeth, aberrant crown and root morphologies, and enamel defects, although the underlying mechanistic link is poorly understood. As most CLP genes are expressed throughout the oral epithelium, the authors hypothesized that the expression of CLP genes may persist in the dental epithelium and thus, in addition to their earlier role in labiopalatine development, may play an important functional role in subsequent tooth patterning and amelogenesis. To address this, the authors generated a unique conditional knockout model involving the major CLP gene, Irf6, that overcomes the previously reported perinatal lethality to enable assessment of any posteruption dental phenotypes. A dental epithelium-specific Irf6 conditional knockout (Irf6-cKO) mouse was generated via a Pitx2-Cre driver line. Dental development was analyzed by microcomputed tomography, scanning electron microscopy, histology, immunohistochemistry, and quantitative polymerase chain reaction. Irf6-cKO mice displayed variable hypodontia, occasional supernumerary incisors and molars, as well as crown and root patterning anomalies, including peg-shaped first molars and taurodontic and C-shaped mandibular second molars. Enamel density was reduced in preeruption Irf6-cKO mice, and some shearing of enamel rods was noted in posteruption incisors. There was also rapid attrition of Irf6-cKO molars following eruption. Histologically, Irf6-cKO ameloblasts exhibited disturbances in adhesion and polarity, and delayed enamel formation was confirmed immunohistochemically. Altered structure of Hertwig's epithelial root sheath was also observed. These data support a role for IRF6 in tooth number, crown and root morphology and amelogenesis that is likely due to a functional role of Irf6 in organization and polarity of epithelial cell types. This data reinforce the notion that various isolated tooth defects could be considered part of the CLP spectrum in relatives of an affected individual.
Study Objectives: This aim of this study was to evaluate oral health and oral health-related quality of life (OHRQoL) in children with obstructive sleep apnea (OSA). Methods: This cross-sectional study involved 31 children who had baseline polysomnography studies and in whom a diagnosis of OSA was made by a sleep physician. They were evaluated against 36 control patients who, based on parent responses to the Pediatric Sleep Questionnaire, were at very low risk for having sleep problems. The mean age of the cohort was 12.3 ± 2.7 years. The oral health status was examined clinically and recorded using caries and periodontal indices. OHRQoL was measured using the Child Oral Health Impact Profile (COHIP) questionnaires. Results: Children with OSA had significantly worsened oral health compared to control patients as evidenced by more caries (15.2 and 3.2, respectively; P < .001) and more periodontitis. Periodontitis severity was measured by the presence of bleeding on probing, (87% versus 30%, P < .001) and higher number of sites with abnormally deep periodontal probing depths (2.7 versus 0.3, P < .001). The COHIP scores were significantly higher among children with OSA compared to control patients, (29.7 versus 11.8, P < .001) consistent with poorer OHRQoL. Conclusions: This study suggests that in children OSA may have a significant association with poorer oral health when compared to control patients without sleep problems, and that their oral health status may have a negative effect on their quality of life. Increased awareness regarding the oral health effects of sleep-disordered breathing in the medical and dental community is needed.
Patients with cleft lip/palate (CLP) have been reported, in some studies, to exhibit an increased prevalence of caries, although the underlying cause for this increase is unknown. In genetically defined mouse models, studies of postnatal sequelae associated with CLP have been hampered by neonatal lethality. Using a conditional targeting approach, we ablated the major CLP gene Irf6 only in the late embryonic oral epithelium ( Irf6 cKO), bypassing the role of the gene in lip and palate morphogenesis and thus ensuring survival to adulthood. We report that Irf6 cKO mice present with 1) dysplastic salivary glands due to disruptions of epithelial junctional complexes, likely secondary to elevated activation of RHO GTPases, and 2) increased salivary cell proliferation. These changes result in significantly reduced saliva flow rate and buffering capacity and increased mucus acidity. A marked decrease in expression of CCL27, one of the major mucosal and skin cytokines, was found that correlated with increased bacterial colonization of the oral cavity with the cariogenic pathogen Streptococcus mutans and other bacteria. When placed on a high-sugar diet, Irf6 cKO mice show a 35-fold increase in presentation and severity of dental caries as compared with wild-type control mice. Strikingly, within the 8-wk test period, many molars extensively dissolved, and there was progressive loss of the alveolar bone, likely as a result of increased colonization of periodontal pathogens. These data provide the first mechanistic insight into the heightened caries susceptibility associated with CLP and indicate a direct role for the major CLP gene Irf6 in salivary gland development and a significant role in regulating oral immunity. Our data suggest that careful evaluation of salivary gland function and the implementation of early oral health preventive strategies are warranted to reduce the burden of dental care in this at-risk population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.