Dataset Information

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

ABSTRACT:

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? 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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7849172 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Chen Yuyi Y Yang Qiudong Q Lv Chunhua C Chen Yue Y Zhao Wenhua W Li Wenlei W Chen Hongyu H Wang Hua H Sun Wen W Yuan Hua H

Cell proliferation 20201231 2

<h4>Objectives</h4>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.<h4>Materials and methods</h4>We used ligature-induced periodontitis models of NLRP3 knockout mice (NLRP3<sup>KO</sup> ) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm-Cre/Rosa<sup>nTnG</sup> mouse to trace ...[more]

PMID: 33382502

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Project description:Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodontitis and the mechanism underlying this process. Methods: An experimental periodontitis model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression levels of oxidative stress, osteogenic, and osteoclastogenic markers in vivo. Cell viability and osteogenic differentiation were analyzed using the Cell Counting Kit-8, alkaline phosphatase, and Alizarin Red staining assays. A reactive oxygen species assay kit, lipid peroxidation MDA assay kit, and western blotting were used to determine oxidative stress status in vitro. To verify the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative regulator, during LIPUS treatment, the siRNA technique and Nrf2-/- mice were used. The PI3K/Akt inhibitor LY294002 was utilized to identify the effects of the PI3K-Akt/Nrf2 signaling pathway. Results: Alveolar bone resorption, which was experimentally induced by periodontitis in vivo, was alleviated by LIPUS via activation of Nrf2. Oxidative stress, induced via H2O2 treatment in vitro, inhibited cell viability and suppressed osteogenic differentiation. These effects were also alleviated by LIPUS treatment via Nrf2 activation. Nrf2 silencing blocked the antioxidant effect of LIPUS by diminishing heme oxygenase-1 expression. Nrf2-/- mice were susceptible to ligature-induced periodontitis, and the protective effect of LIPUS on alveolar bone dysfunction was weaker in these mice. Activation of Nrf2 by LIPUS was accompanied by activation of the PI3K/Akt pathway. The oxidative defense function of LIPUS was inhibited by exposure to LY294002 in vitro. Conclusions: These results demonstrated that LIPUS regulates alveolar bone homeostasis in periodontitis by attenuating oxidative stress via the regulation of PI3K-Akt/Nrf2 signaling. Thus, Nrf2 plays a pivotal role in the protective effect exerted by LIPUS against ligature-induced experimental periodontitis.

Dataset Information

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

Objectives

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

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