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FoxO1 knockdown inhibits RANKL-induced osteoclastogenesis by blocking NLRP3 inflammasome activation.
Wang, Zhanqi; Luo, Wenxin; Zhang, Guorui; Li, Haiyun; Zhou, Feng; Wang, Dongyang; Feng, Xuan; Xiong, Yi; Wu, Yingying.
Afiliação
  • Wang Z; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Luo W; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Zhang G; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Li H; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Zhou F; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Wang D; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Feng X; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Xiong Y; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Wu Y; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article