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

Objectives 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. Materials and methods We used ligature-induced periodontitis models of NLRP3 knockout mice (NLRP3(KO)) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm-Cre/Rosa(nTnG) 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. Results Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3(KO) 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(nTnG) 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-1 beta activation and osteoclast differentiation in ligature-induced periodontitis. Conclusion Our findings reveal that NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.

Automated summary

The study demonstrates that NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation. MCC950 can inhibit the differentiation of osteoclast precursors and reduce the number of Lysm-Cre(+) osteoclast precursors in periodontitis, leading to significant suppression of alveolar bone loss.