The Role of Epithelial <b><i>Stat3</i></b> in Amelogenesis during Mouse Incisor Renewal

Abstract

The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14^Cre/+;Stat3^fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis.

Intraoral and maxillofacial abnormalities in patients with autosomal dominant hyper-IgE syndrome

“…All previous studies reported a high frequency of persistent primary teeth with delayed primary tooth exfoliation and permanent tooth eruption [11,12,15,16,22]. It was already shown that STAT3 has a role in amelogenesis, pulp stem cell differentiation, and bone development [29]. The lack of late eruption of permanent teeth or the lack of persistence of primary teeth can be attributed to regular dental care, namely the extraction of teeth to prevent further complications.…”

Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

“…This implied that the enamel formation from endothelial cells was also influenced by Stat3-deficient dental mesenchyme. Similarly, Bin Zhang et al reported that the loss of Stat3 in dental endothelial cells ( Krt14 - Cre ; Stat3 fl/fl ) caused delayed incisor amelogenesis and dentin abnormalities [ 16 ]. Signals from the dental mesenchyme have been shown to affect HRES in several mouse knockout studies, further supporting our hypothesis [ 24 – 26 ].…”

“…Our previous studies reported that loss of Stat3 in mesenchyme exhibited skeletal malformations and mineralization abnormalities in mice [ 13 , 14 ]. As some studies reported, Stat3 is expressed in dental epithelial cells and odontoblasts during tooth development [ 15 , 16 ]. Bin Zhang et al .…”

“…Bin Zhang et al . reported that loss of Stat3 in epithelial cells resulted in delayed enamel mineralization in mouse incisors [ 16 ]. These studies suggested that Stat3 is important for the development of bone and teeth.…”