Activated Epithelial FGF8 Signaling Induces Fused Supernumerary Incisors

FGF8, which is specifically expressed in the dental epithelium prior to the E12.5 bud stage, is a key player during odontogenesis, being responsible for the initiation of tooth development. Here, to investigate the impact of persistent FGF8 signaling on tooth development, we forcibly activated FGF8 signaling in the dental epithelium after the bud stage by generating K14-Cre;R26R-Fg8 mice. We found that a unique type of fused supernumerary incisors is formed, although morphologically resembling the features of type II dens invaginatus in humans. Further analysis revealed that ectopically activated epithelial FGF8 alters the cell fate of the incisor lingual outer enamel epithelium, endowing it with odontogenic potential by the activation of several key tooth genes, including Pitx2, Sox2, Lef-1, p38, and Erk1/2, and induces de novo formation of an extra incisor crown lingually in parallel to the original one, leading to the formation of an extra incisor crown and fused with the original incisor eventually. Meanwhile, the overdosed epithelial FGF8 signaling dramatically downregulates the expression of mesenchymal Bmp4, leading to severely impaired enamel mineralization. Based on the location of the extra incisors, we propose that they are likely to be rescued replacement teeth. Our results further demonstrate the essential role of FGF8 signaling for tooth initiation and the establishment of progenitor cells of dental epithelial stem cells during development.

Bilateral ectopic third molar in the maxillary sinuses associated with dentigerous cyst: a case report

A dentigerous cyst is an epithelial-lined odontogenic cyst formed by an accumulation of fluid between the reduced enamel epithelium and the crown of an unerupted tooth. About 70% of dentigerous cysts occur in the mandible and 30% in the maxilla and the most involved teeth are maxillary canines and maxillary third molar. Dentigerous cysts often displace the related tooth into an ectopic position. In the maxilla when the cyst expands into the sinus, usually causes total or partial occupation of the sinus cavity and can extend to the nose. We report a rare case of a 24-year-old female with bilateral maxillary third molars inside the maxillary sinuses attached to a dentigerous cyst and treated with a minimally invasive endoscopic surgery through the middle meatal meatotomy.

Signaling Modulation by miRNA-221-3p During Tooth Morphogenesis in Mice

miRNAs are conserved short non-coding RNAs that play a role in the modulation of various biological pathways during tissue and organ morphogenesis. In this study, the function of miRNA-221-3p in tooth development, through its loss or gain in function was evaluated. A variety of techniques were utilized to evaluate detailed functional roles of miRNA-221-3p during odontogenesis, including in vitro tooth cultivation, renal capsule transplantation, in situ hybridization, real-time PCR, and immunohistochemistry. Two-day in vitro tooth cultivation at E13 identified altered cellular events, including cellular proliferation, apoptosis, adhesion, and cytoskeletal arrangement, with the loss and gain of miRNA-221-3p. qPCR analysis revealed alterations in gene expression of tooth-related signaling molecules, including β-catenin, Bmp2, Bmp4, Fgf4, Ptch1, and Shh, when inhibited with miRNA-221-3p and mimic. Also, the inhibition of miRNA-221-3p demonstrated increased mesenchymal localizations of pSMAD1/5/8, alongside decreased expression patterns of Shh and Fgf4 within inner enamel epithelium (IEE) in E13 + 2 days in vitro cultivated teeth. Moreover, 1-week renal transplantation of in vitro cultivated teeth had smaller tooth size with reduced enamel and dentin matrices, along with increased cellular proliferation and Shh expression along the Hertwig epithelial root sheath (HERS), within the inhibitor group. Similarly, in 3-week renal calcified teeth, the overexpression of miRNA-221-3p did not affect tooth phenotype, while the loss of function resulted in long and slender teeth with short mesiodistal length. This study provides evidence that a suitable level of miRNA-221-3p is required for the modulation of major signaling pathways, including Wnt, Bmp, and Shh, during tooth morphogenesis.

The Sonic Hedgehog–Patched–Gli Signaling Pathway Maintains Dental Epithelial and Pulp Stem/Progenitor Cells and Regulates the Function of Odontoblasts

This study aimed to elucidate the role of the Sonic hedgehog (Shh)–Patched (Ptch)–Gli signaling pathway in maintaining dental epithelial and pulp stem/progenitor cells and regulating the function of odontoblasts. Doxycycline (dox)-inducible histone 2B (H2B)–green fluorescent protein (GFP) transgenic mice ingested dox at prenatal embryonic days 14.5 or 15.5 and their offspring were collected from postnatal day 1 (P1) to week 3 (P3W). Immunohistochemistry for Gli1, Ptch1, and Ptch2 and in situ hybridization for Shh and Ptch1 were conducted. Mandibular incisors of postnatal day 2 H2B-GFP transgenic and wild-type mice were cultivated in a nutrient medium with Shh antibody for 4 days and subsequently processed for immunohistochemistry for Sox2. In molars, dense H2B-GFP-label-retaining cells (H2B-GFP-LRCs) were densely distributed throughout the dental pulp during P1 to postnatal week 2 (P2W) and decreased in number by postnatal P3W, whereas the number of dense H2B-GFP-LRCs in the subodontoblastic layer increased in number at P2W. Gli1+ and Pthc1+ cells were distributed throughout the enamel organ and dental pulp, including the odontoblast and subodontoblastic layers. Shh mRNA was expressed in the inner enamel epithelium and shifted into odontoblasts after dentin deposition. Ptch1 mRNA was expressed in the inner enamel epithelium and cuspal pulpal tissue on P1 and decreased in intensity from postnatal week 1 to P3W. In incisors, the apical bud contained H2B-GFP-LRCs, Gli1+ cells, and Ptch1+ cells. The addition of Shh antibody to explants induced a decrease in the number of Sox2+ cells due to the increase in apoptotic cells in the apical bud. Thus, the Shh–Ptch–Gli signaling pathway plays a role in maintaining quiescent adult stem cells and regulating the function of odontoblasts.

Management of Dentigerous Cyst: A Review Article

Introduction: Dentigerous cyst is a pathological epithelial cavity that surrounds an unerupted tooth crown. Dentigerous cysts are usually associated with impacted teeth, mandibular third molars, first and second premolars and canines. Dentigerous cysts can occur at any age, but most cases of these cysts occur at the age of approximately 20 years. Men are affected more often than women. Purpose.To find out how the mechanism of dentigerous cysts. The cyst cavity is lined with epithelial cells derived from the epithelial enamel that is reduced from the tooth-forming organs. According to its pathogenesis, the pressure exerted by an erupted tooth on the follicle can block venous flow leading to accumulation of exudate between the reduced enamel epithelium and the crown of the tooth. These cysts are mostly due to fluid accumulation either between the reduced enamel epithelium and the enamel or between the layers of the enamel organ. This fluid accumulation occurs as a result of the pressure exerted by the erupting tooth on the affected follicle, which blocks venous flow, thus inducing rapid transudation of serum in the capillary walls. Discussion: The expansion of the dentigerous cyst causes the release of bone resorbing factor and an increase in the osmolarity of the cyst fluid as a result of the discharge of inflammatory cells, the discharge of residual epithelial enamel and tooth enamel, and desquamation of epithelial cells into the lumen of the cyst. In theory, the fluid will cause cystic proliferation. because the hyperosmolar content produced by cellular breakdown and cell products causes an osmotic gradient to pump fluid into the lumen of the cyst or it can also be said that an increase in the osmolarity of cyst fluid is the result of a shortcut to inflammatory cells and desquamation of epithelial cells into the lumen of the cyst resulting in a dentigerous cyst. Conclusion: The dentigerous cysts that surround the unerupted dental crowns are caused by the accumulation of fluid either between the reduced enamel epithelium or between the layers of the enamel organs. Dentigerous cysts can cause infection, pain, swelling, root dislocation, and resorption of adjacent tooth roots.

Dentigerous cyst arising from a denticle in a primary teeth- a rare case report with brief review of literature

Odontogenic cysts are derived from odontogenic epithelium which may develop before or after the formation of tooth. Most of these are developmental in origin. While dentigerous cysts are common odontogenic cysts that are related to the crown of the impacted tooth and known to arise from reduced enamel epithelium.