{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:14:03Z","timestamp":1791000843174,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,3,10]],"date-time":"2019-03-10T00:00:00Z","timestamp":1552176000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400523"],"award-info":[{"award-number":["81400523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570987"],"award-info":[{"award-number":["81570987"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601909"],"award-info":[{"award-number":["81601909"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81621062"],"award-info":[{"award-number":["81621062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81520108009"],"award-info":[{"award-number":["81520108009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>In this study, we investigate the mechanistic link between rheumatoid arthritis (RA) and periodontitis to identify a novel target (cathepsin K; Ctsk) for the treatment of comorbid periodontitis and RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An experimental model of periodontitis with arthritis was established in DBA\/1 mice. We then tested the effect of BML\u2010244, a specific inhibitor of Ctsk, by quantifying several inflammatory markers of TLR9 signalling both in vivo and in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that periodontitis\u2013rheumatoid arthritis comorbidity causes severer periodontal bone and joint cartilage destruction than either disease alone. Inhibition of Ctsk reduced infiltration by dendritic cells and T cells and inflammatory cytokine production; these improvements alleviated the hard\u2010tissue erosion in periodontitis and RA as measured by bone erosion in periodontal lesions and cartilage destruction in knee joints. Inhibition of Ctsk also decreased the expression of TLR4 and TLR9 in vivo, whereas in vitro experiments indicated that Ctsk is involved specifically in the production of cytokines in response to TLR9 engagement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data reveal that periodontitis and RA may have additive pathological effects through dysregulation of the TLR9 pathway and that Ctsk is a critical mediator of this pathway and contributes to the pathogenesis of RA and periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.13060","type":"journal-article","created":{"date-parts":[[2019,1,13]],"date-time":"2019-01-13T10:51:15Z","timestamp":1547376675000},"page":"286-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Inhibition of Ctsk alleviates periodontitis and comorbid rheumatoid arthritis via downregulation of the TLR9 signalling pathway"],"prefix":"10.1111","volume":"46","author":[{"given":"Weiyi","family":"Pan","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuwei","family":"Yin","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Xue","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyu","family":"Lu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Handong","family":"Ding","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neel R.","family":"Nabar","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-9131","authenticated-orcid":false,"given":"Liang","family":"Hao","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0b013e3180690616"},{"key":"e_1_2_8_3_1","volume-title":"Standardized relative quantification of immunofluorescence tissue staining [Protocol PDF file]","author":"Arqu\u00e9s O.","year":"2012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150110"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2008.00448.x"},{"key":"e_1_2_8_6_1","first-page":"817","article-title":"Radiographic scoring methods as outcome measures in rheumatoid arthritis: Properties and advantages","volume":"60","author":"Boini S.","year":"2001","journal-title":"Annals of the Rheumatic Diseases"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.173"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21273"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2009.00544.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00814-16"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.02.025"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.28"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.3.478"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100682"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512468757"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115091109"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker257"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200002)43:2<250::AID-ANR3>3.0.CO;2-P"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.140643"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.04.008"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510760112"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100266"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel065"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.6.1693"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.400655"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058599"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513483142"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00733-06"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.185"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00424-15"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0901-1"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000082462.26258.FE"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.4.487"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.139"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00756-12"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2001.72.6.779"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-009-0194-9"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0103-64402009000500001"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.070501"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20678"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2005.00689.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520290310001646668"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23224"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/337181a0"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12468"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2006.00585.x"}],"container-title":["Journal of Clinical Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcpe.13060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.13060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcpe.13060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.13060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T17:27:10Z","timestamp":1694194030000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcpe.13060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/jcpe.13060"],"URL":"https:\/\/doi.org\/10.1111\/jcpe.13060","archive":["Portico"],"relation":{},"ISSN":["0303-6979","1600-051X"],"issn-type":[{"value":"0303-6979","type":"print"},{"value":"1600-051X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}