NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>We used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3<jats:sup>KO</jats:sup>) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/Rosa<jats:sup>nTnG</jats:sup> mouse to trace the changes of Lysm‐Cre<jats:sup>+</jats:sup> 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3<jats:sup>KO</jats:sup> 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<jats:sup>nTnG</jats:sup> mice to demonstrate that MCC950 decreases the number of Lysm‐Cre<jats:sup>+</jats:sup> 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.</jats:p></jats:sec>