Periodontitis is an oral chronic inflammatory disease that is initiated by periodontal microbial communities and requires disruption of the homeostatic responses. The prevalence of periodontal disease increases with age; more than 70% of adults 65 years and older have periodontal disease. A pathogenic microbial community is required for initiating periodontal disease. Dysbiotic immune-inflammatory response and bone remodeling are characteristics of periodontitis. The transcription factor forkhead box protein O1 (FOXO1) is a key regulator of a number of cellular processes, including cell survival and differentiation, immune status, reactive oxygen species (ROS) scavenging, and apoptosis. Although accumulating evidence indicates that FOXO1 activity can be induced by periodontal pathogens, the roles of FOXO1 in periodontal homeostasis and disease have not been well documented. The present review summarizes how the FOXO1 signaling axis can regulate periodontal bacteria-epithelial interactions, immune-inflammatory response, bone remodeling, and wound healing.

Tooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig’s epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

Aim: To date, controversies still exist regarding the exact cellular origin and regulatory mechanisms of periodontium development, which hinders efforts to achieve ideal periodontal tissue regeneration. Axin2-expressing cells in the periodontal ligament (PDL) have been shown to be a novel progenitor cell population that is essential for periodontal homeostasis. In the current study, we aimed to elucidate the regulatory role of bone morphogenetic protein receptor type 1A (BMPR1A)-mediated BMP signalling in Axin2-expressing cells during periodontium development.Materials and Methods: Two strains of Axin2 gene reporter mice, Axin2 lacZ/+ and Axin2 CreERT2/+ ; R26R tdTomato/+ mice, were used. We next generated Axin2 CreERT2/+ ; R26R DTA/+ ; R26R tdTomato/+ mice to genetically ablate of Axin2-lineage cells. Axin2 CreERT2/+ ; Bmpr1a fl/fl ; R26R tdTomato/+ mice were established to conditionally knock out Bmpr1a in Axin2-lineage cells. Multiple approaches, including microcomputed tomography, calcein green, and alizarin red double-labelling, scanning electron microscopy, and histological and immunostaining assays, were used to analyse periodontal phenotypes and molecular mechanisms.Results: X-gal staining revealed that Axin2-expressing cells in the PDL were mainly distributed along the alveolar bone and cementum surface. Cell lineage tracing and cell ablation assays further demonstrated the indispensable role of Axin2-expressing cells in periodontium development. Next, we found that conditional knockout of Bmpr1a in Axin2-lineage cells led to periodontal defects, which were characterized by alveolar bone loss, impaired cementogenesis, and abnormal Sharpey's fibres.Conclusions: Our findings suggest that Axin2-expressing cells in the PDL are essential for periodontium development, which is regulated by BMP signalling.

Objectives Nuclear factor I‐C (NFIC) plays a critical role in regulating epithelial‐mesenchymal crosstalk during tooth development. However, it remains largely unknown about how NFIC functions in dentin and enamel formation. In the present review, we aim to summarize the most recent discoveries in the field and gain a better understanding of the roles NFIC performs during tooth formation. Subjects and Methods Nfic−/− mice exhibit human dentin dysplasia type I (DDI)‐like phenotypes signified by enlarged pulp chambers, the presence of short‐root anomaly, and failure of odontoblast differentiation. Although loss of NFIC has little effect on molar crown morphology, researchers have detected aberrant microstructures of enamel in the incisors. Recently, accumulating evidence has further uncovered the novel function of NFIC in the process of enamel and dentin formation. Results During epithelial‐mesenchyme crosstalk, the expression of NFIC is under the control of SHH‐PTCH‐SMO‐GLI1 pathway. NFIC is closely involved in odontoblast lineage cells proliferation and differentiation, and the maintenance of NFIC protein level in cytoplasm is negatively regulated by TGF‐β signaling pathway. In addition, NFIC has mild effect on ameloblast differentiation, enamel mineralization and cementum formation. Conclusions NFIC plays an important role in tooth development and is required for the formation of dentin, enamel as well as cementum.