{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:12:50Z","timestamp":1790021570679,"version":"4.0.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> This paper briefly reviews the structure and function of NLRP3 inflammasomes, signaling pathway, relationship with synovitis in KOA, and intervention of traditional Chinese medicine (TCM) in NLRP3 inflammasomes as a means to improve its therapeutic potential and clinical application.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> Literatures about NLRP3 inflammasomes and synovitis in KOA were reviewed to analyze and discuss.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> NLRP3 inflammasome can activate NF-\u03baB mediated signal transduction, which in turn causes the expression of proinflammatory cytokines, initiates the innate immune response, and triggers synovitis in KOA. The TCM monomer\/active ingredient, decoction, external ointment, and acupuncture regulating NLRP3 inflammasomes are helpful to alleviate synovitis in KOA.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The NLRP3 inflammasome plays a significant role in the pathogenesis of synovitis in KOA, TCM intervention targeting the NLRP3 inflammasome can be a novel approach and therapeutic direction for the treatment of synovitis in KOA.<\/jats:p>","DOI":"10.3389\/fgene.2023.1159167","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T05:33:45Z","timestamp":1680068025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention"],"prefix":"10.3389","volume":"14","author":[{"given":"Xianfu","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingpeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.bbrc.2016.02.039","article-title":"Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis","volume":"472","author":"Aibibula","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.14336\/AD.2019.1127","article-title":"Pyroptosis plays a role in osteoarthritis","volume":"11","author":"An","year":"2020","journal-title":"Aging Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1093\/rheumatology\/ker524","article-title":"Microcrystals as DAMPs and their role in joint inflammation","volume":"51","author":"Busso","year":"2012","journal-title":"Rheumatol. Oxf."},{"key":"B4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.visres.2020.09.008","article-title":"Flexible face processing: Holistic processing of facial identity is modulated by task-irrelevant facial expression","volume":"178","author":"Chen","year":"2020","journal-title":"Eur. J. Inflamm."},{"key":"B5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s13075-019-2085-6","article-title":"Inhibition of Nrf2\/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis","volume":"21","author":"Chen","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1472567","DOI":"10.1155\/2016\/1472567","article-title":"The overexpression of NALP3 inflammasome in knee osteoarthritis is associated with synovial membrane prolidase and NADPH oxidase 2","volume":"2016","author":"Clavijo-Cornejo","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1007\/s00011-021-01493-8","article-title":"Blockade of macrophage-associated programmed death 1 inhibits the pyroptosis signalling pathway in sepsis","volume":"70","author":"Fu","year":"2021","journal-title":"Inflamm. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jhep.2020.07.041","article-title":"Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis","volume":"74","author":"Gaul","year":"2021","journal-title":"J. Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12866-019-1404-z","article-title":"Osteopontin in the host response to Leishmania amazonensis","volume":"19","author":"Giraud","year":"2019","journal-title":"BMC Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/cei.13167","article-title":"NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis","volume":"194","author":"Guo","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5182","DOI":"10.1038\/s41467-018-07573-4","article-title":"NLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathway","volume":"9","author":"Hafner-Bratkovi\u010d","year":"2018","journal-title":"Nat. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.molimm.2022.01.002","article-title":"miR-223 in exosomes from bone marrow mesenchymal stem cells ameliorates rheumatoid arthritis via downregulation of NLRP3 expression in macrophages","volume":"143","author":"Huang","year":"2022","journal-title":"Mol. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1038\/s41423-021-00740-6","article-title":"NLRP3 inflammasome activation and cell death","volume":"18","author":"Huang","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"14867","DOI":"10.1073\/pnas.1111101108","article-title":"NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy","volume":"108","author":"Jin","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: An overview of mechanisms of activation and regulation overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s13063-015-0726-x","article-title":"Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): Study protocol for a randomized controlled trial","volume":"16","author":"Leung","year":"2015","journal-title":"Trials"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1111\/exd.14412","article-title":"Mdivi-1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome","volume":"30","author":"Li","year":"2021","journal-title":"Exp. Dermatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"106745","DOI":"10.1016\/j.intimp.2020.106745","article-title":"Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1\u03b1\/NLRP3 inflammasome signaling","volume":"86","author":"Li","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"741","DOI":"10.3969\/j.issn.1008-0805","article-title":"Experimental research on the inhibition of NLRP3 inflammasome activation and improvement of knee osteoarthritis by Layers Adjusting External Application","volume":"31","author":"Li","year":"","journal-title":"Lishizhen Med. Materia Medica Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.2147\/DDDT.S261216","article-title":"Chrysin attenuates the NLRP3 inflammasome cascade to reduce synovitis and pain in KOA rats","volume":"14","author":"Liao","year":"2020","journal-title":"Drug Des. Devel Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.6039\/j.issn.1001-0408","article-title":"Discussion on the mechanism of synovitis of KOA relieved by\u201cSanse Powder\u201dVolatile Oil based on the activation of NLRP3 inflammasome","volume":"32","author":"Liao","year":"2021","journal-title":"China Pharm."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.3969\/j.issn.1001-1978","article-title":"Isochlorogenic acid A inhibits activation of NLRP3\/NF-\u03baB in rats with collagen-induced arthritis","volume":"35","author":"Liu","year":"2019","journal-title":"Chin. Pharmacol. Bull."},{"key":"B23","doi-asserted-by":"publisher","first-page":"739644","DOI":"10.3389\/fphar.2021.739644","article-title":"Interventional efects of the topical of \"sanse powder\" essential Oils nanoemulsion on knee osteoarthritis inRats by targeting the ERS\/TXNIP\/NLRP3 signaling Axis","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1652244","DOI":"10.1155\/2022\/1652244","article-title":"Corilagin restrains NLRP3 inflammasome activation and pyroptosis through the ROS\/TXNIP\/NLRP3 pathway to prevent inflammation","volume":"2022","author":"Luo","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4537","DOI":"10.2147\/JIR.S371536","article-title":"Characterization of cathepsin B in mediating silica nanoparticle-induced macrophage pyroptosis via an NLRP3-dependent manner","volume":"15","author":"Ma","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"599022","DOI":"10.3389\/fphar.2020.599022","article-title":"Vanillic acid reduces pain-related behavior in knee osteoarthritis rats through the inhibition of NLRP3 inflammasome-related synovitis","volume":"11","author":"Ma","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/s1097-2765(02)00599-3","article-title":"The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: Current understanding with therapeutic implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.cmet.2020.07.016","article-title":"The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation","volume":"32","author":"McGettrick","year":"2020","journal-title":"Cell Metab."},{"key":"B30","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41590-022-01192-4","article-title":"Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome","volume":"23","author":"Moretti","year":"2022","journal-title":"Nat. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1870579","DOI":"10.1155\/2022\/1870579","article-title":"Knock down of LMX1B suppressed cell apoptosis and inflammatory response in IL-1\u03b2-induced human osteoarthritis chondrocytes through NF-\u03baB and NLRP3 signal pathway","volume":"2022","author":"Mu","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"B32","doi-asserted-by":"publisher","first-page":"11282","DOI":"10.1073\/pnas.1117765109","article-title":"Critical role for calcium mobilization in activation of the NLRP3 inflammasome","volume":"109","author":"Murakami","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B33","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3390\/life11040303","article-title":"Tread mill exercise after controlled abnormal joint movement inhibits cartilage degeneration and synovitis","volume":"11","author":"Oka","year":"2021","journal-title":"Life (Basel)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"8400496","DOI":"10.1155\/2022\/8400496","article-title":"Salvianolic acid B attenuates iopromide-induced renal tubular epithelial cell injury by inhibiting the TLR4\/NF-\u03baB\/NLRP3 signaling pathway","volume":"2022","author":"Pei","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"767512","DOI":"10.3389\/fimmu.2021.767512","article-title":"The expression of inflammasomes NLRP1 and NLRP3, toll-like receptors, and vitamin D receptor in synovial fibroblasts from patients with different types of knee arthritis","volume":"12","author":"Sakalyte","year":"2022","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1080\/08916934.2022.2093861","article-title":"Knockdown of NEK7 alleviates anterior cruciate ligament transection osteoarthritis (ACLT)-induced knee osteoarthritis in mice via inhibiting NLRP3 activation","volume":"55","author":"Sun","year":"2022","journal-title":"Autoimmunity"},{"key":"B37","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/jcp.26011","article-title":"Histomorphology and innate immunity during the progression of osteoarthritis: Does synovitis affect cartilage degradation","volume":"233","author":"Wang","year":"2018","journal-title":"J. Cell Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3921021","DOI":"10.1155\/2022\/3921021","article-title":"Effects of moxibustion combined with ultrashort wave on pain and oxidative stress in elderly patients with knee osteoarthritis","volume":"2022","author":"Wang","year":"","journal-title":"Comput. Math. Methods Med."},{"key":"B40","first-page":"8742","article-title":"Galangin attenuates IL-1\u03b2-induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis","volume":"13","author":"Wang","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"5476064","DOI":"10.1155\/2020\/5476064","article-title":"Electroacupuncture alleviates osteoarthritis by suppressing NLRP3 inflammasome activation in Guinea pigs","volume":"2020","author":"Wang","year":"","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3892\/mmr.2020.11736","article-title":"Relationship between the pyroptosis of fibroblast like synoviocytes and HMGB1 secretion in knee osteoarthritis","volume":"23","author":"Xiao","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"101548","DOI":"10.1016\/j.trim.2022.101548","article-title":"Andrographolide suppresses osteoarthritis progression by regulating circ_Rapgef1\/miR-383-3p\/NLRP3 signaling axis","volume":"71","author":"Yan","year":"2022","journal-title":"Transpl. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"109349","DOI":"10.1016\/j.intimp.2022.109349","article-title":"Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1\/ROS\/NLRP3 axis","volume":"113","author":"Yi","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"471","DOI":"10.13702\/j.1000-0607.20211269","article-title":"Effect of electroacupuncture on pyroptosis of synovial tissues in rats with knee osteoarthritis","volume":"47","author":"Yu","year":"2022","journal-title":"Zhen Ci Yan Jiu"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.3389\/fimmu.2019.02538","article-title":"Pharmacological inhibitors of the NLRP3 inflammasome","volume":"10","author":"Zahid","year":"2019","journal-title":"Front. Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12974-022-02445-7","article-title":"Extracellular vesicles derived from mesenchymal stem cells alleviate neuroinflammation and mechanical allodynia in interstitial cystitis rats by inhibiting NLRP3 inflammasome activation","volume":"19","author":"Zhang","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"B48","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.intimp.2018.09.001","article-title":"Baicalin exerts neuroprotective effects via inhibiting activation of GSK3\u03b2\/NF-\u03baB\/NLRP3 signal pathway in a rat model of depression","volume":"64","author":"Zhang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1186\/s13287-021-02640-y","article-title":"Caspase-3\/NLRP3 signaling in the mesenchymal stromal niche regulates myeloid-biased hematopoiesis","volume":"12","author":"Zhang","year":"","journal-title":"Stem Cell Res. Ther."},{"key":"B50","doi-asserted-by":"publisher","first-page":"5534614","DOI":"10.1155\/2021\/5534614","article-title":"Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through the inhibition of HIF-1\u03b1 and NLRP3 inflammasome","volume":"2021","author":"Zhang","year":"","journal-title":"Mediat. Inflamm."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2165918","DOI":"10.1155\/2019\/2165918","article-title":"Inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in knee osteoarthritis","volume":"2019","author":"Zhang","year":"","journal-title":"Mediat. Inflamm."},{"key":"B52","doi-asserted-by":"publisher","first-page":"6326517","DOI":"10.1155\/2019\/6326517","article-title":"Increased HIF-1\u03b1 in knee osteoarthritis aggravate synovial fibrosis via fibroblast-like synoviocyte pyroptosis","volume":"2019","author":"Zhang","year":"","journal-title":"Oxid. Med. Cell Longev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"68","DOI":"10.14148\/j.issn.1672-0482","article-title":"Mitigation effect of xibining on synovitis of knee osteoarthritis based on the activation of NLRP3 inflammasomes in hypoxic tissue","volume":"36","author":"Zhang","year":"2020","journal-title":"J. Nanjing Univ. Tradit. Chin. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"643149","DOI":"10.3389\/fimmu.2021.643149","article-title":"Inflammasomes and fibrosis","volume":"12","author":"Zhang","year":"","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2671","DOI":"10.1084\/jem.20162040","article-title":"Protein kinase D at the Golgi controls NLRP3 inflammasome activation","volume":"214","author":"Zhang","year":"2017","journal-title":"J. Exp. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"767","DOI":"10.7644\/j.issn.1674-9960","article-title":"Xanthotoxol against knee osteoarthritis in rats by inhibiting inflammation: An experimental study","volume":"43","author":"Zhuang","year":"2019","journal-title":"Mil. Med. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"888306","DOI":"10.3389\/fimmu.2022.888306","article-title":"Inflammatory response to regulated cell death in gout and its functional implications","volume":"13","author":"Zhao","year":"","journal-title":"Front. Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.3892\/mmr.2018.8520","article-title":"NLRP1 and NLRP3 inflammasomes mediate LPS\/ATP induced pyroptosis in knee osteoarthritis","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1136\/annrheumdis-2021-221985","article-title":"Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity","volume":"81","author":"Zhao","year":"","journal-title":"Ann. Rheum. Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"767","DOI":"10.7644\/j.issn.1674-9960","article-title":"Xanthotoxol against knee osteoarthritis in rats by inhibiting inflammation: An experimental study","volume":"43","author":"Zhuang","year":"2019","journal-title":"Mil. Med. Sci."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1159167\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T05:33:53Z","timestamp":1680068033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1159167\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":60,"alternative-id":["10.3389\/fgene.2023.1159167"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1159167","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]},"article-number":"1159167"}}