Welcome to JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCES) June 12, 2025
WANG Jia-he, ZOU Shu-juan, XIE Jing, et al. Latest Findings on NOD-Like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome and Bone and Articular Diseases[J]. Journal of Sichuan University (Medical Sciences), 2023, 54(3): 679-684. DOI: 10.12182/20230560105
Citation: WANG Jia-he, ZOU Shu-juan, XIE Jing, et al. Latest Findings on NOD-Like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome and Bone and Articular Diseases[J]. Journal of Sichuan University (Medical Sciences), 2023, 54(3): 679-684. DOI: 10.12182/20230560105

Latest Findings on NOD-Like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome and Bone and Articular Diseases

More Information
  • Corresponding author:

    ZHOU Chen-chen, E-mail: chenchenzhou5510@scu.edu.cn

  • Received Date: August 14, 2022
  • Revised Date: April 02, 2023
  • Available Online: May 19, 2023
  • Published Date: May 19, 2023
  • Inflammasomes are important components of the innate immune system. They are assembled by cytoplasmic pattern recognition receptors and play a critical role in the pathogenesis and progression of various inflammatory diseases through regulating the release and activation of inflammatory cytokines and inducing cell prytosis. NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome has been widely studied and has been shown to be closely associated with cardiovascular diseases and metabolic disorders. Bone and joint diseases, such as osteoarthritis and rheumatoid arthritis show high prevalence worldwide and can cause bone and cartilage damage, pain, and dysfunction, adversely affecting the patients' quality of life. The reported findings of some studies indicate that the pathogenesis of various bone and articular diseases is associated with NLRP3 inflammasome. Small molecule antagonists targeting NLRP3 inflammasome have shown considerable therapeutic potentials, but their clinical application still needs further exploration. Herein, we reviewed the composition and function of NLRP3 inflammasome and its association with bone and articular diseases.
  • [1]
    MARTINON F, BURNS K, TSCHOPP J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell,2002,10(2): 417–426. DOI: 10.1016/s1097-2765(02)00599-3
    [2]
    BROZ P, DIXIT V M. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol,2016,16(7): 407–420. DOI: 10.1038/nri.2016.58
    [3]
    RATHINAM V A, FITZGERALD K A. Inflammasome complexes: emerging mechanisms and effector functions. Cell,2016,165(4): 792–800. DOI: 10.1016/j.cell.2016.03.046
    [4]
    PAIK S, KIM J K, SILWAL P, et al. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol,2021,18(5): 1141–1160. DOI: 10.1038/s41423-021-00670-3
    [5]
    Von MOLTKE J, AYRES J S, KOFOED E M, et al. Recognition of bacteria by inflammasomes. Annu Rev Immunol,2013,31: 73–106. DOI: 10.1146/annurev-immunol-032712-095944
    [6]
    SWANSON K V, DENG M, TING J P. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol,2019,19(8): 477–489. DOI: 10.1038/s41577-019-0165-0
    [7]
    XUE Y, ENOSI TUIPULOTU D, TAN W H, et al. Emerging activators and regulators of inflammasomes and pyroptosis. Trends Immunol,2019,40(11): 1035–1052. DOI: 10.1016/j.it.2019.09.005
    [8]
    SMOLEN J S, ALETAHA D, BARTON A, et al. Rheumatoid arthritis. Nat Rev Dis Primers,2018,4: 18001. DOI: 10.1038/nrdp.2018.1
    [9]
    KOLLY L, BUSSO N, PALMER G, et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium. Immunology,2010,129(2): 178–185. DOI: 10.1111/j.1365-2567.2009.03174.x
    [10]
    ROSENGREN S, HOFFMAN H M, BUGBEE W, et al. Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis,2005,64(5): 708–714. DOI: 10.1136/ard.2004.025577
    [11]
    CHOULAKI C, PAPADAKI G, REPA A, et al. Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis. Arthritis Res Ther,2015,17: 257. DOI: 10.1186/s13075-015-0775-2
    [12]
    ZHANG Y, ZHENG Y, LI H. NLRP3 inflammasome plays an important role in the pathogenesis of collagen-induced arthritis. Mediators Inflamm,2016,2016: 9656270. DOI: 10.1155/2016/9656270
    [13]
    GUO C, FU R, WANG S, et al. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis. Clin Exp Immunol,2018,194(2): 231–243. DOI: 10.1111/cei.13167
    [14]
    DONG X, ZHENG Z, LIN P, et al. ACPAs promote IL-1beta production in rheumatoid arthritis by activating the NLRP3 inflammasome. Cell Mol Immunol,2020,17(3): 261–271. DOI: 10.1038/s41423-019-0201-9
    [15]
    MATMATI M, JACQUES P, MAELFAIT J, et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet,2011,43(9): 908–912. DOI: 10.1038/ng.874
    [16]
    VANDE WALLE L, Van OPDENBOSCH N, JACQUES P, et al. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature,2014,512(7512): 69–73. DOI: 10.1038/nature13322
    [17]
    LAM I K Y, CHOW J X, LAU C S, et al. MicroRNA-mediated immune regulation in rheumatic diseases. Cancer Lett,2018,431: 201–212. DOI: 10.1016/j.canlet.2018.05.044
    [18]
    LI X F, SHEN W W, SUN Y Y, et al. MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes. Joint Bone Spine,2016,83(6): 695–700. DOI: 10.1016/j.jbspin.2015.10.007
    [19]
    HUANG Y, LU D, MA W, et al. miR-223 in exosomes from bone marrow mesenchymal stem cells ameliorates rheumatoid arthritis via downregulation of NLRP3 expression in macrophages. Mol Immunol,2022,143: 68–76. DOI: 10.1016/j.molimm.2022.01.002
    [20]
    LI Y, ZHENG J Y, LIU J Q, et al. Succinate/NLRP3 inflammasome induces synovial fibroblast activation: therapeutical effects of clematichinenoside AR on arthritis. Front Immunol,2016,7: 532. DOI: 10.3389/fimmu.2016.00532
    [21]
    HONG Z, ZHANG X, ZHANG T, et al. The ROS/GRK2/HIF-1alpha/NLRP3 pathway mediates pyroptosis of fibroblast-like synoviocytes and the regulation of monomer derivatives of paeoniflorin. Oxid Med Cell Longev,2022,2022: 4566851. DOI: 10.1155/2022/4566851
    [22]
    HAN X, LIN D, HUANG W, et al. Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: a review of TCM intervention. Front Genet,2023,14: 1159167. DOI: 10.3389/fgene.2023.1159167
    [23]
    WOJDASIEWICZ P, PONIATOWSKI L A, SZUKIEWICZ D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm,2014,2014: 561459. DOI: 10.1155/2014/561459
    [24]
    DERFUS B A, KURIAN J B, BUTLER J J, et al. The high prevalence of pathologic calcium crystals in pre-operative knees. J Rheumatol,2002,29(3): 570–574.
    [25]
    PAZAR B, EA H K, NARAYAN S, et al. Basic calcium phosphate crystals induce monocyte/macrophage IL-1beta secretion through the NLRP3 inflammasome in vitro. J Immunol,2011,186(4): 2495–2502. DOI: 10.4049/jimmunol.1001284
    [26]
    DENOBLE A E, HUFFMAN K M, STABLER T V, et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci U S A,2011,108(5): 2088–2093. DOI: 10.1073/pnas.1012743108
    [27]
    MARCHETTI C, SWARTZWELTER B, KOENDERS M I, et al. NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. Arthritis Res Ther,2018,20(1): 169. DOI: 10.1186/s13075-018-1664-2
    [28]
    CHENG F, YAN F F, LIU Y P, et al. Dexmedetomidine inhibits the NF-kappaB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats. Pharm Biol,2019,57(1): 649–659. DOI: 10.1080/13880209.2019.1651874
    [29]
    STAROBOVA H, NADAR E I, VETTER I. The NLRP3 Inflammasome: Role and Therapeutic Potential in Pain Treatment. Front Physiol,2020,11: 1016. DOI: 10.3389/fphys.2020.01016
    [30]
    SHAO M, LV D, ZHOU K, et al. Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway. Pharm Biol,2022,60(1): 535–542. DOI: 10.1080/13880209.2022.2042327
    [31]
    LI W, WANG Y, TANG Y, et al. Quercetin alleviates osteoarthritis progression in rats by suppressing inflammation and apoptosis via inhibition of IRAK1/NLRP3 signaling. J Inflamm Res,2021,14: 3393–3403. DOI: 10.2147/JIR.S311924
    [32]
    HE M, LU B, OPOKU M, et al. Metformin prevents or delays the development and progression of osteoarthritis: new insight and mechanism of action. Cells,2022,11(19): 3012. DOI: 10.3390/cells11193012
    [33]
    LORDEN G, SANJUAN-GARCIA I, De PABLO N, et al. Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation. J Exp Med,2017,214(2): 511–528. DOI: 10.1084/jem.20161452
    [34]
    HOFMANN S R, KUBASCH A S, IOANNIDIS C, et al. Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1beta expression and release. Clin Immunol,2015,161(2): 300–307. DOI: 10.1016/j.clim.2015.09.013
    [35]
    BRANDT D, SOHR E, PABLIK J, et al. CD14(+) monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression. Clin Immunol,2018,196: 77–84. DOI: 10.1016/j.clim.2018.04.011
    [36]
    SCIANARO R, INSALACO A, BRACCI LAUDIERO L, et al. Deregulation of the IL-1beta axis in chronic recurrent multifocal osteomyelitis. Pediatr Rheumatol Online J,2014,12: 30. DOI: 10.1186/1546-0096-12-30
    [37]
    DASARI T K, GEIGER R, KARKI R, et al. The nonreceptor tyrosine kinase SYK drives caspase-8/NLRP3 inflammasome-mediated autoinflammatory osteomyelitis. J Biol Chem,2020,295(11): 3394–3400. DOI: 10.1074/jbc.RA119.010623
    [38]
    XUE F, SHU R, XIE Y. The expression of NLRP3, NLRP1 and AIM2 in the gingival tissue of periodontitis patients: RT-PCR study and immunohistochemistry. Arch Oral Biol,2015,60(6): 948–958. DOI: 10.1016/j.archoralbio.2015.03.005
    [39]
    SURLIN P, LAZAR L, SINCAR C, et al. NLRP3 inflammasome expression in gingival crevicular fluid of patients with periodontitis and chronic hepatitis C. Mediators Inflamm,2021,2021: 6917919. DOI: 10.1155/2021/6917919
    [40]
    ISOLA G, POLIZZI A, SANTONOCITO S, et al. Periodontitis activates the NLRP3 inflammasome in serum and saliva. J Periodontol,2022,93(1): 135–145. DOI: 10.1002/JPER.21-0049
    [41]
    HIENZ S A, PALIWAL S, IVANOVSKI S. Mechanisms of Bone Resorption in Periodontitis. J Immunol Res,2015,2015: 615486. DOI: 10.1155/2015/615486
    [42]
    MURAKAMI T, TAKAHATA Y, HATA K, et al. Role of interleukin-1 and inflammasomes in oral disease. J Oral Biosci,2020,62(3): 242–248. DOI: 10.1016/j.job.2020.07.003
    [43]
    MONTENEGRO RAUDALES J L, YOSHIMURA A, SM Z, et al. Dental calculus stimulates interleukin-1beta secretion by activating NLRP3 Inflammasome in human and mouse phagocytes. PLoS One,2016,11(9): e0162865. DOI: 10.1371/journal.pone.0162865
    [44]
    YAMAGUCHI Y, KURITA-OCHIAI T, KOBAYASHI R, et al. Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease. Inflamm Res,2017,66(1): 59–65. DOI: 10.1007/s00011-016-0992-4
    [45]
    LIAN D, DAI L, XIE Z, et al. Periodontal ligament fibroblasts migration injury via ROS/TXNIP/Nlrp3 inflammasome pathway with Porphyromonas gingivalis lipopolysaccharide. Mol Immunol,2018,103: 209–219. DOI: 10.1016/j.molimm.2018.10.001
    [46]
    ZHAO P, LIU J, PAN C, et al. NLRP3 inflammasome is required for apoptosis of Aggregatibacter actinomycetemcomitans-infected human osteoblastic MG63 cells. Acta Histochem,2014,116(7): 1119–1124. DOI: 10.1016/j.acthis.2014.05.008
    [47]
    KELK P, MOGHBEL N S, HIRSCHFELD J, et al. Aggregatibacter actinomycetemcomitans leukotoxin activates the NLRP3 inflammasome and cell-to-cell communication. Pathogens,2022,11(2): 159. DOI: 10.3390/pathogens11020159
    [48]
    CHEN Y, YANG Q, LV C, et al. NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation. Cell Prolif,2021,54(2): e12973. DOI: 10.1111/cpr.12973
    [49]
    KAWAHARA Y, KANEKO T, YOSHINAGA Y, et al. Effects of sulfonylureas on periodontopathic bacteria-induced inflammation. J Dent Res,2020,99(7): 830–838. DOI: 10.1177/0022034520913250
    [50]
    CHAUHAN D, VANDE WALLE L, LAMKANFI M. Therapeutic modulation of inflammasome pathways. Immunol Rev,2020,297(1): 123–138. DOI: 10.1111/imr.12908
  • Cited by

    Periodical cited type(10)

    1. 马纪龙,刘洋,谢兴文,李宁,齐鹏. 川芎活性成分治疗膝关节炎药理研究进展. 中国骨质疏松杂志. 2025(02): 236-241 .
    2. 丁恺志,龚妍春,李晓诺,朱袁婕,姚丽华. NLRP3炎性小体在肌肉骨骼系统疾病中的作用. 生物工程学报. 2024(02): 337-349 .
    3. 魏洁雅,徐思群,周学东,谢静. 牙槽骨修复重建分子调控机制的研究新进展. 四川大学学报(医学版). 2024(01): 31-38 .
    4. 吴东明,董金莉,谈平. 谈平教授治疗类风湿关节炎临床经验. 中国医药导报. 2024(07): 139-143 .
    5. 龙自祥,罗春山,蒲兴魏,欧阳北平,彭阳阳,何瑾江,陆廷盛. 术前血清TGF-β1、HMGB1、NLRP3对脊柱骨折合并脊髓损伤患者预后的预测价值. 现代生物医学进展. 2024(11): 2073-2078 .
    6. 徐磊,赵润平,陈洁云,杨艳鲜,郭锡龙,代敏,田国宝,秦丽娜. 基于CUMS模型探究抑郁症对细菌感染的影响及作用(英文). 中山大学学报(医学科学版). 2024(04): 567-581 .
    7. 王志云,韩树峰,魏金政,刘超,赵巍. NLRP3炎症小体与类风湿关节炎患者疾病活动度和骨代谢指标的关系及其诊断价值分析. 现代生物医学进展. 2024(14): 2672-2676 .
    8. 何鹏,李秀成,何争珍,周显臣. 鹰嘴豆素A对骨关节炎的体外作用机制研究. 局解手术学杂志. 2024(09): 753-758 .
    9. 谢宇涵,黄程程,阮文秀,李洋. 中药干预NLR P3炎性小体防治炎症性关节炎的研究进展. 中国骨与关节杂志. 2024(11): 950-954 .
    10. 武君珂,张芳芳,黄丽平,许妍妍,李遇伯,王玉明,谭宸琛. 基于NLRP3介导细胞焦亡在类风湿性关节炎中的机制及中医药研究进展. 中草药. 2024(24): 8632-8643 .

    Other cited types(1)

Catalog

    Article views (618) PDF downloads (45) Cited by(11)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return