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

• Published in: Cell proliferation Vol. 54; no. 2; pp. e12973 - n/a
• Main Authors: Chen, Yuyi, Yang, Qiudong, Lv, Chunhua, Chen, Yue, Zhao, Wenhua, Li, Wenlei, Chen, Hongyu, Wang, Hua, Sun, Wen, Yuan, Hua
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2021; John Wiley and Sons Inc
• Subjects: Alveolar bone; alveolar bone loss; Alveolar Bone Loss - metabolism; Alveolar Bone Loss - pathology; Alveolar Bone Loss - prevention & control; Animal models; Animals; Antibodies; Biomedical materials; Bone loss; Cell Differentiation - drug effects; Differentiation; Disease Models, Animal; Flow cytometry; Gum disease; Heterocyclic Compounds, 4 or More Rings - pharmacology; Heterocyclic Compounds, 4 or More Rings - therapeutic use; Immune system; inflammasome; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - metabolism; Inflammatory diseases; Innate immunity; Interleukin-1beta - metabolism; Laboratory animals; Lipopolysaccharides - pharmacology; MCC950; Membranes; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Original; osteoclast differentiation; Osteoclastogenesis; Osteoclasts; Osteoclasts - cytology; Osteoclasts - metabolism; Osteogenesis - drug effects; Osteoprogenitor cells; Penicillin; Periodontitis; Periodontitis - drug therapy; Periodontitis - etiology; Periodontitis - pathology; Phenotypes; Phosphatase; Precursors; Proteins; R&D; Research & development; Software; Statistical analysis; Stem Cells - cytology; Stem Cells - metabolism; Sulfones - pharmacology; Sulfones - therapeutic use; Tomography; NLRP3; alveolar bone loss; MCC950; osteoclast differentiation; inflammasome; periodontitis
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12973

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 (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.
Results
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.
Conclusion
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.