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Suppression of the NLRP3 Inflammasome through Activation of the Transient Receptor Potential Channel Melastatin 2 Promotes Osteogenesis in Tooth Extraction Sockets of Periodontitis

  • Qin Li
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Haicheng Wang
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Liwei Liu
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Yuteng Weng
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Shuyu Xu
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Lin Li
    Affiliations
    Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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  • Zuolin Wang
    Correspondence
    Address correspondence to Zuolin Wang.
    Affiliations
    Department of Oral and Maxillofacial Surgery and Department of Oral Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
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Published:November 18, 2022DOI:https://doi.org/10.1016/j.ajpath.2022.10.009
      We aimed to explore the involvement of transient receptor potential channel melastatin 2 (TRPM2)-mediated activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in osteogenesis in the healing process of tooth extraction sockets. Tooth extraction socket tissue samples were collected from patients with and without periodontitis. A TRPM2 knockout mouse model of socket healing with or without periodontitis and their wild-type littermates were used for comparing socket healing phenotypes. Micro–computed tomography imaging and three-dimensional reconstruction of the sockets were performed. Hematoxylin and eosin staining was performed for histopathologic analysis. Immunofluorescence, immunohistochemistry, and Western blot analysis were used for evaluation of protein expression; the mRNA levels were evaluated by quantitative RT-PCR. Osteogenic, chondrogenic, and adipogenic differentiation potential of human bone marrow mesenchymal stem cells (BMMSCs) was evaluated, and calcium deposition was evaluated using Alizarin Red S staining. NLRP3 and CASP1 were up-regulated in tooth sockets of periodontitis patients. NLRP3 knockdown promoted the osteogenic differentiation of maxillary BMMSCs under inflammatory conditions. TRPM2 was significantly up-regulated in the tooth extraction socket tissue of periodontitis. Inhibiting TRPM2 expression mitigated the NLRP3 inflammasome and its deleterious effect on osteogenesis. Activation of the TRPM2 ion channel regulated osteogenesis of BMMSCs under inflammatory conditions via Ca2+ influx, the mitochondrial dynamics, and pyroptosis. Targeting the TRPM2/Ca2+/NLRP3 axis could be beneficial in the healing process of the tooth extraction sockets of patients with periodontitis.
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