NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides.
NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides.
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DOI：
10.3390/ijms23116096
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发表时间：
2022-05-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
在炎症性骨疾病如牙周炎中，核苷酸结合寡聚化结构域、富含亮氨酸的重复序列和含有pyrin结构域3（NLRP 3）的炎性体通过促进促炎细胞因子IL-1β的产生来加速骨吸收。然而，NLRP 3炎性体在生理性骨重建中的作用仍不清楚。在这里，我们研究了它在破骨细胞生成中的作用，在存在和不存在脂多糖（LPS），革兰氏阴性细菌成分。当骨髓巨噬细胞（BMSCs）与核因子-κB配体（RANKL）的受体激活剂在NLRP 3炎性体抑制剂的存在下处理时，破骨细胞形成在LPS不存在下促进，但在其存在下减弱。用RANKL和LPS处理的BMPs产生IL-1β，IL-1受体拮抗剂抑制破骨细胞生成，表明IL-1β参与。单独使用RANKL处理的贝伐单抗不产生IL-1β，但增加了活性氧（ROS）的产生。ROS抑制剂抑制了含有半胱天冬酶-1募集结构域（ASC）斑点形成的凋亡相关斑点样蛋白，NLRP 3炎性体抑制剂消除了RANKL处理的Bcirrhosis中的细胞毒性，表明RANKL通过ROS激活NLRP 3炎性体诱导Bcirrhosis中的pyroptotic细胞死亡。这表明NLRP 3炎性体在感染条件下通过IL-1β的产生促进破骨细胞生成，但在生理条件下通过诱导破骨细胞前体的焦亡抑制破骨细胞生成。
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-1β 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-κB 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-1β, and IL-1 receptor antagonist inhibited osteoclastogenesis, indicating IL-1β involvement. BMMs treated with RANKL alone produced no IL-1β 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-1β production under infectious conditions, but suppresses osteoclastogenesis by inducing pyroptosis in osteoclast precursors under physiological conditions.
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影响因子：
5.6
作者：
Mae M;Alam MI;Yamashita Y;Ozaki Y;Higuchi K;Ziauddin SM;Montenegro Raudales JL;Sakai E;Tsukuba T;Yoshimura A
通讯作者：
Yoshimura A
影响因子：
3.7
作者：
Montenegro Raudales JL;Yoshimura A;Sm Z;Kaneko T;Ozaki Y;Ukai T;Miyazaki T;Latz E;Hara Y
通讯作者：
Hara Y
影响因子：
13.5
作者：
Wree, Alexander;Eguchi, Akiko;McGeough, Matthew D.;Pena, Carla A.;Johnson, Casey D.;Canbay, Ali;Hoffman, Hal M.;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
口腔骨微生物学：口腔微生物群在牙槽骨稳态中的作用
影响因子：
5.7
作者：
Cheng X;Zhou X;Liu C;Xu X
通讯作者：
Xu X
DOI：
10.1196/annals.1365.035
发表时间：
2006-01-01
期刊：
WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES
影响因子：
--
作者：
Hadjidakis, Dimitrios J.;Androulakis, Ioannis I.
通讯作者：
Androulakis, Ioannis I.