Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Cell Prolif. 2021 Feb;54(2):e12973. doi: 10.1111/cpr.12973. Epub 2020 Dec 31.
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 (NLRP3 ) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm-Cre/Rosa 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 NLRP3 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/Rosa 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 炎性小体是先天免疫系统的关键部分，在多种炎症性疾病中发挥重要作用。然而，NLRP3 炎性小体对牙周炎的影响尚未得到充分研究。
我们使用 NLRP3 基因敲除（NLRP3 ）小鼠及其野生型（WT）同窝仔鼠的结扎诱导牙周炎模型，比较其牙槽骨表型。我们进一步使用 Lysm-Cre/Rosa 小鼠，追踪有或没有 MCC950 治疗的结扎诱导牙周炎中 Lysm-Cre 破骨细胞前体的变化。最后，我们探讨了 MCC950 作为一种治疗牙周炎的潜在药物在体内和体外的作用。
在这里，我们通过结扎诱导牙周炎模型显示，与 WT 同窝仔鼠相比，NLRP3 基因敲除（NLRP3 ）小鼠的破骨细胞前体数量、破骨细胞分化和牙槽骨丢失减少。接下来，我们使用 NLRP3 炎性小体的特异性抑制剂 MCC950 抑制破骨细胞前体分化为破骨细胞。此外，我们使用 Lysm-Cre/Rosa 小鼠证明，MCC950 可减少结扎诱导牙周炎中 Lysm-Cre 破骨细胞前体的数量。最后，MCC950 治疗可显著抑制牙槽骨丢失，减少 IL-1β 激活和结扎诱导牙周炎中的破骨细胞分化。
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诱导牙周炎中的牙槽骨丢失。
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