Wnt1's Differential Effects on Craniofacial Bone and Tooth Development

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00144367" target="_blank" >RIV/00216224:14110/25:00144367 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.sagepub.com/doi/10.1177/00220345251336191" target="_blank" >https://journals.sagepub.com/doi/10.1177/00220345251336191</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/00220345251336191" target="_blank" >10.1177/00220345251336191</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Wnt1's Differential Effects on Craniofacial Bone and Tooth Development

Popis výsledku v původním jazyce

The development of craniofacial bones and teeth relies heavily on the Wnt signaling pathway, yet the specific mechanisms and Wnt variants involved remain under continual investigation. Using publicly available single-cell sequencing data from the mouse incisor, we reveal Wnt1 expression across dental structures and investigate its role using a Col1a1-dependent Wnt1 transgenic mouse model. Inducing Wnt1 early on affects craniofacial bone without disturbing tooth development, but prolonged embryonic induction leads to postnatal mortality with osteopetrosis-like bone overgrowth and malformed teeth. While tooth formation was initially unaffected by postnatal Wnt1 induction, prolonged activation impaired tooth root formation and odontoblast differentiation, resulting in shortened roots and thinner dentin. Three-dimensional micro-computed tomography quantification reveal that both embryonic and postnatal activation of Wnt1 significantly increase neural crest-derived craniofacial bone volume, whereas mesenchymal-derived craniofacial bones are unaffected. Importantly, osteoclastogenesis is suppressed by Wnt1 in a dose-dependent manner, revealed through bulk RNA sequencing and in vitro experiments. These findings emphasize the differential effects of Wnt1 on bone development based on origin and highlight its role in modulating osteoclast activity, indicating broader implications for craniofacial development and potential therapeutic avenues.

Název v anglickém jazyce

Wnt1's Differential Effects on Craniofacial Bone and Tooth Development

Popis výsledku anglicky

The development of craniofacial bones and teeth relies heavily on the Wnt signaling pathway, yet the specific mechanisms and Wnt variants involved remain under continual investigation. Using publicly available single-cell sequencing data from the mouse incisor, we reveal Wnt1 expression across dental structures and investigate its role using a Col1a1-dependent Wnt1 transgenic mouse model. Inducing Wnt1 early on affects craniofacial bone without disturbing tooth development, but prolonged embryonic induction leads to postnatal mortality with osteopetrosis-like bone overgrowth and malformed teeth. While tooth formation was initially unaffected by postnatal Wnt1 induction, prolonged activation impaired tooth root formation and odontoblast differentiation, resulting in shortened roots and thinner dentin. Three-dimensional micro-computed tomography quantification reveal that both embryonic and postnatal activation of Wnt1 significantly increase neural crest-derived craniofacial bone volume, whereas mesenchymal-derived craniofacial bones are unaffected. Importantly, osteoclastogenesis is suppressed by Wnt1 in a dose-dependent manner, revealed through bulk RNA sequencing and in vitro experiments. These findings emphasize the differential effects of Wnt1 on bone development based on origin and highlight its role in modulating osteoclast activity, indicating broader implications for craniofacial development and potential therapeutic avenues.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30208 - Dentistry, oral surgery and medicine

Projekt

<a href="/cs/project/GA23-06160S" target="_blank" >GA23-06160S: Fluktuace mikroprostředí kmenových buněk jako zdroj tkáňové adaptability ve zdraví a nemoci</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

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1415-1424

Kód UT WoS článku

001500237400001

EID výsledku v databázi Scopus

2-s2.0-105008065551