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FoxO1 knockdown inhibits RANKL‐induced osteoclastogenesis by blocking NLRP3 inflammasome activation.

Authors :
Wang, Zhanqi
Luo, Wenxin
Zhang, Guorui
Li, Haiyun
Zhou, Feng
Wang, Dongyang
Feng, Xuan
Xiong, Yi
Wu, Yingying
Source :
Oral Diseases. Jul2024, Vol. 30 Issue 5, p3272-3285. 14p.
Publication Year :
2024

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 and Methods: 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1354523X
Volume :
30
Issue :
5
Database :
Academic Search Index
Journal :
Oral Diseases
Publication Type :
Academic Journal
Accession number :
178532324
Full Text :
https://doi.org/10.1111/odi.14800