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NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation
Authors:Yuyi Chen  Qiudong Yang  Chunhua Lv  Yue Chen  Wenhua Zhao  Wenlei Li  Hongyu Chen  Hua Wang  Wen Sun  Hua Yuan
Institution:1. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing China ; 2. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing China ; 3. Department of Stomatology, Taizhou People’s Hospital of Jiangsu Province, Taizhou China ; 4. Department of Basic Science of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing China
Abstract:ObjectivesNLRP3 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.Materials and methodsWe 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.ResultsHere, 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.ConclusionOur findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.
Keywords:alveolar bone loss  inflammasome  MCC950  NLRP3  osteoclast differentiation  periodontitis
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