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

Chen, Yuyi; Yang, Qiudong; Lv, Chengyin; Chen, Yue; Zhao, Wenhua; Li, Wenlei; Chen, Hongyu; Wang, Hua; Sun, Wen; Yuan, Hua

doi:10.1111/cpr.12973

Cited by 100 publications

(83 citation statements)

References 39 publications

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“…Additionally, Gal-3 activates the NLRP3 inflammasome [7,8], capable of converting pro-IL-1β to IL-1β, an important inflammatory mediator that participates in inflammatory processes and is implicated in periodontal tissue destruction [30]. Moreover, high expression of NLRP3 and IL-1β has been found in human gingival tissues with severe chronic periodontitis [31]. NLRP3 is highly expressed in monocytes/macrophages [32] and influences their differentiation in osteoclasts [31], with induction of bone resorption.…”

Section: Discussionmentioning

confidence: 99%

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Next-Generation Sequencing Analysis of Root Canal Microbiota Associated with a Severe Endodontic-Periodontal Lesion

et al. 2021

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A patient with an unusual endo-periodontal lesion, without coronal decay or damage, likely caused by a deep periodontal lesion with subsequent endodontic bacterial migration, required medical care. Next-generation sequencing (NGS) was used to assess the endodontic microbiota in vestibular and palatal canals after tooth extraction, evidencing a predominant population (Fusobacterium nucleatum) in one endodontic canal, and a mixed bacterial population with six major populations almost equally distributed in the other endodontic canal (F. nucleatum, Porphyromonas gingivalis, P. endodontis, Parvimonas, Peptostreptococcus stomatis, Prevotella multiformis). These data could suggest different, separated ecologic niches in the same endodontic system, with potentially different pathogenicity levels, clinical manifestations and prognoses for every single canal of the same tooth.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, high expression of NLRP3 and IL-1β has been found in human gingival tissues with severe chronic periodontitis [31]. NLRP3 is highly expressed in monocytes/macrophages [32] and influences their differentiation in osteoclasts [31], with induction of bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing Analysis of Root Canal Microbiota Associated with a Severe Endodontic-Periodontal Lesion

et al. 2021

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“…The MCC950-treated periodontitis group had a lower number of Lysm-Cre + cells compared to the vehicle-treated periodontitis group. Therefore, NLRP3 deficiency and MCC950 reduced the number of osteoclast precursors and prevented osteoclastogenesis [62].…”

Section: Osteoclastsmentioning

confidence: 97%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

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Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

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“…NLRP3 expression in GCF and periodontal parameters were increased in patients with chronic periodontitis compared to those in healthy individuals but then decreased after 6 months of combined periodontal-orthodontic treatment ( 234 ). Knockout of the Nlrp3 gene or treatment with an NLRP3 inhibitor significantly reduces the number and differentiation of osteoclasts, thereby decreasing alveolar bone loss in mice with ligature-induced periodontitis ( 179 ). Periodontal pathogens and their by-products can also trigger inflammatory responses associated with NLRP3 inflammasome signaling ( 180 , 235 , 236 ).…”

Section: Inflammasomes In Inflammatory Osteolysis Of the Alveolar Bone And Jawsmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

2021

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 100 publications

References 39 publications

Next-Generation Sequencing Analysis of Root Canal Microbiota Associated with a Severe Endodontic-Periodontal Lesion

Next-Generation Sequencing Analysis of Root Canal Microbiota Associated with a Severe Endodontic-Periodontal Lesion

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Inflammasomes in Alveolar Bone Loss

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