FoxO1 knockdown inhibits RANKL-induced osteoclastogenesis by blocking NLRP3 inflammasome activation.
Oral Dis
; 2023 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-37927112
ABSTRACT
OBJECTIVES:
This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. MATERIALS ANDMETHODS:
A conventional ligature-induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA-seq) was performed to explore the underlying mechanisms of FoxO1 knockdown-mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay.RESULTS:
FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation-related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA-seq revealed that the nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1-knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation.CONCLUSIONS:
FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF-κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article