{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T21:43:33Z","timestamp":1779399813187,"version":"3.53.1"},"reference-count":74,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Emerging studies have shown that immune response to biomaterial implants plays a central role in bone healing. Ipriflavone is clinically used for osteoporosis. However, the mechanism of ipriflavone in immune response to implants in early stages of osseointegration remains unclear. In this study, we aimed to investigate the potential role of ipriflavone in early bone healing process and uncover the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We carried out histological examination as well as analysis of proinflammatory cytokines and NLRP3 inflammasome activation in a tibial implantation mouse model with intra\u2010peritoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites, characterized by reductions of inflammatory cell infiltration and proinflammatory cytokine interleukin\u20101\u03b2 levels. Ipriflavone treatment also showed beneficial effects on early osseointegration. Further investigations of the molecular mechanism showed that the suppression of NLRP3 inflammasome acts upstream of NLRP3 oligomerization through abrogating the production of reactive oxygen species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results revealed an anti\u2010inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This study provides a new strategy for the development of immune\u2010regulated biomaterials and treatment options for NLRP3\u2010related diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.13647","type":"journal-article","created":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T08:44:22Z","timestamp":1652604262000},"page":"814-827","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ipriflavone suppresses <scp>NLRP3<\/scp> inflammasome activation in host response to biomaterials and promotes early bone healing"],"prefix":"10.1111","volume":"49","author":[{"given":"Yun","family":"Chen","sequence":"first","affiliation":[{"name":"School\/Hospital of Stomatology Zhejiang Chinese Medical University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Shi","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Ning","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences Zhejiang Chinese Medical University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Feng","sequence":"additional","affiliation":[{"name":"School\/Hospital of Stomatology Zhejiang Chinese Medical University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Lin","sequence":"additional","affiliation":[{"name":"School\/Hospital of Stomatology Zhejiang Chinese Medical University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuming","family":"He","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Xie","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12632"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cid.12711"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.11.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.02.010"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092080114"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0338"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0501.2003.00972.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.10.025"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2018.10.019"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano10122573"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900377"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12973"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2015.11.004"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.08.015"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/342304"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1718"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.0022-0337.2003.67.8.tb03681.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20020240"},{"key":"e_1_2_11_20_1","first-page":"798","article-title":"Histopathologic observations on early oral implant failures","volume":"14","author":"Esposito M.","year":"1999","journal-title":"The International Journal of Oral & Maxillofacial Implants"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.013"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.05.078"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150237"},{"key":"e_1_2_11_24_1","first-page":"4669","article-title":"Ipriflavone promotes osteogenesis of MSCs derived from osteoporotic rats","volume":"22","author":"Gao A. G.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425917738331"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12254"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.008"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4690-x"},{"key":"e_1_2_11_29_1","first-page":"10","article-title":"Ipriflavone: An important bone\u2010building isoflavone","volume":"4","author":"Head K. A.","year":"1999","journal-title":"Alternative Medicine Review"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2257"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(20000605)50:3<365::AID-JBM10>3.0.CO;2-X"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708689"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.001"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171419"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.12.004"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0764-x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq431"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01717"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.09.010"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0276-5"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn203596e"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105152108"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cid.13009"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2009.07.050"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3704"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2019.110229"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.016"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cden.2014.12.003"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v013a01"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.08.006"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-6009(08)80099-2"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/782382"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694696"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12370"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.648809"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00335.2012"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.02.004"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0501.2011.02327.x"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7120526"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/cid.12274"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.12.009"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.04.035"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S163956"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2020.07.001"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.09.023"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2021.111992"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-008-9265-2"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13837"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237929"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.09.010"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2015.10.036"}],"container-title":["Journal of Clinical Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.13647","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcpe.13647","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.13647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T05:14:04Z","timestamp":1692854044000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcpe.13647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":74,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1111\/jcpe.13647"],"URL":"https:\/\/doi.org\/10.1111\/jcpe.13647","archive":["Portico"],"relation":{},"ISSN":["0303-6979","1600-051X"],"issn-type":[{"value":"0303-6979","type":"print"},{"value":"1600-051X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"assertion":[{"value":"2021-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}