Vascular Invasion of the Dental Epithelium Is Essential for Ameloblasts

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10500008" target="_blank" >RIV/00216208:11110/25:10500008 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YXfsP54sXC" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YXfsP54sXC</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/00220345251341850" target="_blank" >10.1177/00220345251341850</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Vascular Invasion of the Dental Epithelium Is Essential for Ameloblasts

Popis výsledku v původním jazyce

The tooth is a highly vascularized organ. During odontogenesis, blood vessels enter the forming tooth through the dental papilla and surround the dental epithelium from the cap stage. We show that during the late bell stage, endothelial cells invade the outer enamel epithelium (OEE) and migrate through the stellate reticulum to vascularize the forming ameloblast layer. This migration was evident in both mouse and human tooth germs and is likely to represent a conserved mechanism. Migration was coordinated by dynamic changes in Vegf expression in the dental epithelium, with expression at the OEE at the bell stage shifting toward the ameloblast layer. Invasion through the OEE involved loss of integrity of the basement membrane, downregulation of tight junctions, and apoptosis of some OEE cells. Changes in the OEE were dependent on Hedgehog signaling, with a failure to invade in K14creSmoothenedfl/fl mice, where epithelial cells cannot respond to Hedgehog signaling. The impact of failed migration through the OEE was followed in Cdh5creERT2 Vegfr2fl/fl mutant mice, where the endothelial cells cannot respond to vascular endothelial growth factor (VEGF). Failure of OEE invasion resulted in differentiation defects and extensive cell death of the ameloblast layer, highlighting the essential requirement for vascularization for development of this layer. Our results reveal the essential role of Hedgehog and VEGF signaling in correct vascularization of the tooth germ epithelial layers, allowing breakdown of the OEE and targeting endothelial cell migration into the epithelium. A better understanding of the molecular regulation of endothelial cells will help decipher how this cell population interacts with different cells of the enamel organ and will aid in attempts to revascularize teeth.

Název v anglickém jazyce

Vascular Invasion of the Dental Epithelium Is Essential for Ameloblasts

Popis výsledku anglicky

The tooth is a highly vascularized organ. During odontogenesis, blood vessels enter the forming tooth through the dental papilla and surround the dental epithelium from the cap stage. We show that during the late bell stage, endothelial cells invade the outer enamel epithelium (OEE) and migrate through the stellate reticulum to vascularize the forming ameloblast layer. This migration was evident in both mouse and human tooth germs and is likely to represent a conserved mechanism. Migration was coordinated by dynamic changes in Vegf expression in the dental epithelium, with expression at the OEE at the bell stage shifting toward the ameloblast layer. Invasion through the OEE involved loss of integrity of the basement membrane, downregulation of tight junctions, and apoptosis of some OEE cells. Changes in the OEE were dependent on Hedgehog signaling, with a failure to invade in K14creSmoothenedfl/fl mice, where epithelial cells cannot respond to Hedgehog signaling. The impact of failed migration through the OEE was followed in Cdh5creERT2 Vegfr2fl/fl mutant mice, where the endothelial cells cannot respond to vascular endothelial growth factor (VEGF). Failure of OEE invasion resulted in differentiation defects and extensive cell death of the ameloblast layer, highlighting the essential requirement for vascularization for development of this layer. Our results reveal the essential role of Hedgehog and VEGF signaling in correct vascularization of the tooth germ epithelial layers, allowing breakdown of the OEE and targeting endothelial cell migration into the epithelium. A better understanding of the molecular regulation of endothelial cells will help decipher how this cell population interacts with different cells of the enamel organ and will aid in attempts to revascularize teeth.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30106 - Anatomy and morphology (plant science to be 1.6)

Projekt

<a href="/cs/project/GA23-06660S" target="_blank" >GA23-06660S: Fyziologická dynamika odontogeneze v kontextu okolních struktur</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Dental Research

ISSN

0022-0345

e-ISSN

1544-0591

Svazek periodika

104

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1547-1555

Kód UT WoS článku

001517996200001

EID výsledku v databázi Scopus

2-s2.0-105010077692