Relevance of Caspase-1 and Nlrp3 Inflammasome on Inflammatory Bone Resorption in A Murine Model of Periodontitis
Relevance of Caspase-1 and Nlrp3 Inflammasome on Inflammatory Bone Resorption in A Murine Model of Periodontitis
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DOI：
10.1038/s41598-020-64685-y
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发表时间：
2020-05-08
影响因子：
4.6
通讯作者：
Rossa Junior, Carlos
中科院分区：
文献类型：
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作者：
Rocha, Fernanda R. G.;Delitto, Andrea E.;Rossa Junior, Carlos
本研究探讨NLRP 3炎性体及其主要效应因子Caspase-1在牙周炎相关炎症和牙槽骨吸收中的作用。将热灭活的伴放线菌聚集杆菌（Aa）注射到野生型（WT）、Nlrp 3-KO和Caspase 1-KO小鼠的牙龈组织中，每周3次（4周）。骨吸收测定μ CT和破骨细胞数测定抗酒石酸酸性磷酸酶（TRAP）染色。组织学评估炎症（H/E染色和CD 45和Ly 6 G的免疫荧光）。体外研究确定了Nlrp 3和Caspase-1在Rankl诱导的破骨细胞分化和活性以及LPS诱导的炎症相关基因表达中的影响。在Casp 1-KO小鼠中骨吸收显著减少，但在Nlrp 3-KO小鼠中没有。Casp 1-KO小鼠破骨细胞数量增加，而炎症浸润或基因表达与WT和Nlrp 3-KO小鼠相似。引人注目的是，从Nlrp 3缺陷的巨噬细胞分化的破骨细胞在体外具有增加的再吸收活性。LPS诱导的IL-10、IL-12和TNF-α的表达在Nlrp 3和Casp 1缺陷型巨噬细胞中显著降低。作为一项初步研究，这些结果表明，Nlrp 3炎性体在体内炎症和骨吸收中不起重要作用，Caspase-1在实验性牙周病中具有促吸收作用。
This study investigates the role of NLRP3 inflammasome and its main effector Caspase-1 in inflammation and alveolar bone resorption associated with periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans (Aa) was injected 3x/week (4 weeks) into gingival tissues of wild-type (WT), Nlrp3-KO and Caspase1-KO mice. Bone resorption was measured by mu CT and osteoclast number was determined by tartrate-resistant acid phosphatase (TRAP) staining. Inflammation was assessed histologically (H/E staining and immunofluorescence of CD45 and Ly6G). In vitro studies determined the influence of Nlrp3 and Caspase-1 in Rankl-induced osteoclast differentiation and activity and on LPS-induced expression of inflammation-associated genes. Bone resorption was significantly reduced in Casp1-KO but not in Nlrp3-KO mice. Casp1-KO mice had increased in osteoclast numbers, whereas the inflammatory infiltrate or on gene expression were similar to those of WT and Nlrp3-KO mice. Strikingly, osteoclasts differentiated from Nlrp3-deficient macrophages had increased resorbing activity in vitro. LPS-induced expression of Il-10, Il-12 and Tnf-alpha was significantly reduced in Nlrp3- and Casp1-deficient macrophages. As an inceptive study, these results suggest that Nlrp3 inflammasome does not play a significant role in inflammation and bone resorption in vivo and that Caspase-1 has a pro-resorptive role in experimental periodontal disease.