Embryonic and postnatal macrophages are essential for dental morphogenesis and self-renewal

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00144390" target="_blank" >RIV/00216224:14110/25:00144390 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Embryonic and postnatal macrophages are essential for dental morphogenesis and self-renewal

Popis výsledku v původním jazyce

The role of macrophages in teeth, beyond their function in innate immunity, remains unexplored. This study demonstrates that macrophages populate dental tissues during early development and increase in number during pre-eruptive stages postnatally. In continuously growing teeth, they are associated with epithelial and mesenchymal stem cell niches throughout lifetime. To investigate their role in development, we genetically disrupted macrophage migration using neural-crest specific Wnt1Cre/Csf1fl/fl and generalCsf1R knockout organisms. This resulted in abnormal dentin and enamel deposition, eruption defects, and early tooth mispatterning. Notably, the phenotype was partially rescued via bone marrow transplantation. In healthy adults, short-term pharmacological depletion of macrophages caused striking but temporary damage of dental tissues. Following treatment, macrophages rapidly repopulated dental tissue and polarized from M0 to M2 reparative state, leading to tissue restoration. Overall, our findings reveal essential role of macrophages in the dental development and patterning of both mesenchymal and epithelial tooth compartments. This non-immune role of dental macrophages is reminiscent of their function in complex tissue regeneration and requires future studies to dissect precise cellular and molecular mechanisms.

Název v anglickém jazyce

Embryonic and postnatal macrophages are essential for dental morphogenesis and self-renewal

Popis výsledku anglicky

The role of macrophages in teeth, beyond their function in innate immunity, remains unexplored. This study demonstrates that macrophages populate dental tissues during early development and increase in number during pre-eruptive stages postnatally. In continuously growing teeth, they are associated with epithelial and mesenchymal stem cell niches throughout lifetime. To investigate their role in development, we genetically disrupted macrophage migration using neural-crest specific Wnt1Cre/Csf1fl/fl and generalCsf1R knockout organisms. This resulted in abnormal dentin and enamel deposition, eruption defects, and early tooth mispatterning. Notably, the phenotype was partially rescued via bone marrow transplantation. In healthy adults, short-term pharmacological depletion of macrophages caused striking but temporary damage of dental tissues. Following treatment, macrophages rapidly repopulated dental tissue and polarized from M0 to M2 reparative state, leading to tissue restoration. Overall, our findings reveal essential role of macrophages in the dental development and patterning of both mesenchymal and epithelial tooth compartments. This non-immune role of dental macrophages is reminiscent of their function in complex tissue regeneration and requires future studies to dissect precise cellular and molecular mechanisms.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10605 - Developmental biology

Projekt

<a href="/cs/project/GA25-18087S" target="_blank" >GA25-18087S: Buněčná podstata hojení zubu</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