NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.
NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.
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NLRP3通过促进破骨细胞分化来调节结扎诱导的牙周炎中的牙槽骨丢失。
DOI：
10.1111/cpr.12973
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发表时间：
2021-03
影响因子：
8.5
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Chen Y;Yang Q;Lv C;Chen Y;Zhao W;Li W;Chen H;Wang H;Sun W;Yuan H
NLRP3炎性小体是先天免疫系统的重要组成部分，在多种炎性疾病中发挥重要作用。然而，NLRP3炎性体对牙周炎的作用尚未得到充分的研究。我们使用NLRP3基因敲除小鼠（NLRP3KO）和野生型小鼠（WT）结扎诱导的牙周炎模型来比较它们的牙槽骨表型。我们进一步使用Lysm - Cre/RosanTnG小鼠，追踪在结扎诱导的牙周炎中，Lysm - Cre+破骨细胞前体在MCC950治疗或不治疗中的变化。最后，我们在体内和体外实验中探索了MCC950作为治疗牙周炎的潜在药物。通过结扎性牙周炎模型，我们发现NLRP3KO小鼠的破骨细胞前体数量、破骨细胞分化和牙槽骨丢失均比WT小鼠减少。接下来，使用NLRP3炎性体的特异性抑制剂MCC950来抑制破骨细胞前体向破骨细胞的分化。此外，我们使用Lysm‐Cre/RosanTnG小鼠来证明MCC950减少了结扎性牙周炎中Lysm‐Cre+破骨细胞前体的数量。最后，在结扎性牙周炎中，MCC950通过降低IL - 1β激活和破骨细胞分化，显著抑制牙槽骨丢失。我们的研究结果表明NLRP3通过促进破骨细胞分化来调节结扎性牙周炎的牙槽骨丢失。NLRP3通过促进破骨细胞分化调节结扎诱导牙周炎的牙槽骨丢失。牙周组织细菌感染导致破骨细胞前体细胞NLRP3炎性体活化，促进破骨细胞分化和牙槽骨吸收。因此，NLRP3炎性体在牙周炎的病理性骨质流失中起着重要作用。MCC950是NLRP3炎性体的特异性抑制剂，可抑制破骨细胞分化，从而减少牙周炎患者的牙槽骨丢失。
NLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied. We used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/RosanTnG mouse to trace the changes of Lysm‐Cre+ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro. Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/RosanTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre+ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis. Our findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation. NLRP3 Regulates Alveolar Bone Loss in Ligature‐induced Periodontitis by Promoting Osteoclastic Differentiation. Bacterial infection in periodontal tissues leads to the activation of NLRP3 inflammasome in osteoclast precursor cells, which promotes osteoclast differentiation and alveolar bone resorption. Thus, NLRP3 inflammasome contribute significantly to the pathologic bone loss in periodontitis. MCC950, a specific inhibitor of the NLRP3 inflammasome, inhibits osteoclast differentiation, thereby reduces alveolar bone loss in periodontitis.
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影响因子：
8.5
作者：
Pan H;Lin Y;Dou J;Fu Z;Yao Y;Ye S;Zhang S;Wang N;Liu A;Li X;Zhang F;Chen D
通讯作者：
Chen D
影响因子：
6.2
作者：
McCall, Samuel H.;Sahraci, Mahnaz;Marriott, Ian
通讯作者：
Marriott, Ian
影响因子：
4.6
作者：
Rocha, Fernanda R. G.;Delitto, Andrea E.;Rossa Junior, Carlos
通讯作者：
Rossa Junior, Carlos
小鼠CRE模型用于研究骨骼疾病。
影响因子：
4.3
作者：
Dallas SL;Xie Y;Shiflett LA;Ueki Y
通讯作者：
Ueki Y
DOI：
10.4049/jimmunol.1001591
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lee B;Kim TH;Jun JB;Yoo DH;Woo JH;Choi SJ;Lee YH;Song GG;Sohn J;Park-Min KH;Ivashkiv LB;Ji JD
通讯作者：
Ji JD