NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides

被引:24
作者
Alam, Mohammad Ibtehaz [1 ]
Mae, Megumi [1 ]
Farhana, Fatima [2 ]
Oohira, Masayuki [1 ]
Yamashita, Yasunori [1 ]
Ozaki, Yukio [1 ]
Sakai, Eiko [2 ]
Yoshimura, Atsutoshi [1 ]
机构
[1] Nagasaki Univ, Dept Periodontol & Endodontol, Grad Sch Biomed Sci, 1-7-1 Sakamoto, Nagasaki 8528588, Japan
[2] Nagasaki Univ, Dept Dent Pharmacol, Grad Sch Biomed Sci, 1-7-1 Sakamoto, Nagasaki 8528588, Japan
基金
日本学术振兴会;
关键词
NLRP3; inflammasome; interleukin-1; beta; bone remodeling; pyroptosis; reactive oxygen species; RANKL; osteoclast; ACTIVATION;
D O I
10.3390/ijms23116096
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
In inflammatory bone diseases such as periodontitis, the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome accelerates bone resorption by promoting proinflammatory cytokine IL-1 beta production. However, the role of the NLRP3 inflammasome in physiological bone remodeling remains unclear. Here, we investigated its role in osteoclastogenesis in the presence and absence of lipopolysaccharide (LPS), a Gram-negative bacterial component. When bone marrow macrophages (BMMs) were treated with receptor activator of nuclear factor-kappa B ligand (RANKL) in the presence of NLRP3 inflammasome inhibitors, osteoclast formation was promoted in the absence of LPS but attenuated in its presence. BMMs treated with RANKL and LPS produced IL-1 beta, and IL-1 receptor antagonist inhibited osteoclastogenesis, indicating IL-1 beta involvement. BMMs treated with RANKL alone produced no IL-1 beta but increased reactive oxygen species (ROS) production. A ROS inhibitor suppressed apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) speck formation and NLRP3 inflammasome inhibitors abrogated cytotoxicity in BMMs treated with RANKL, indicating that RANKL induces pyroptotic cell death in BMMs by activating the NLRP3 inflammasome via ROS. This suggests that the NLRP3 inflammasome promotes osteoclastogenesis via IL-1 beta production under infectious conditions, but suppresses osteoclastogenesis by inducing pyroptosis in osteoclast precursors under physiological conditions.
引用
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页数:15
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