{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:14:21Z","timestamp":1790100861307,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemophilic arthropathy (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) is characterized by chronic proliferative synovitis leading to cartilage destruction and shares some pathological features with rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). Apoptosis has been implicated in <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> pathogenesis, and an agonistic anti\u2010Fas monoclonal antibody (<jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b) was found to induce <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> fibroblast\u2010like synoviocyte (<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>) apoptosis and suppress synovial hyperplasia in animal models of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>. The aim of this study was to evaluate the effect of anti\u2010Fas <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b on <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> were isolated from knee synovial biopsies from six <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> patients, six <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients and six healthy subjects. The expression of Fas in synovial biopsies was investigated by immunohistochemistry. <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> were stimulated with anti\u2010Fas <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b at different concentrations, alone or in combination with tumour necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1) and basic fibroblast growth factor (<jats:styled-content style=\"fixed-case\">bFGF<\/jats:styled-content>). Fas expression in <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> was assessed by Western blot. Cell viability was studied with the <jats:styled-content style=\"fixed-case\">WST<\/jats:styled-content>\u20101 assay. Active caspase\u20103 levels were measured using <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and Western blot. A strong Fas\u2010immunoreactivity was observed in different cells of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> synovium, including <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>, inflammatory cells and endothelial cells. Fas antigen was constitutively overexpressed in cultured <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>. Anti\u2010Fas <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b had a significant cytotoxicity on <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> in a dose\u2010dependent manner, either alone or in combination with <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 and <jats:styled-content style=\"fixed-case\">bFGF<\/jats:styled-content>. These cytotoxic effects were due to the ability of anti\u2010Fas to induce <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> apoptosis, as shown by the increased active caspase\u20103 levels. Anti\u2010Fas <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b exhibited a more pronounced pro\u2010apoptotic effect on <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> than <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>. Fas antigen is highly expressed on <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> and its stimulation by anti\u2010Fas <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b may be an effective strategy to induce <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content> apoptosis.<\/jats:p>","DOI":"10.1111\/hae.12304","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T09:28:27Z","timestamp":1384939707000},"source":"Crossref","is-referenced-by-count":5,"title":["Agonistic anti\u2010human Fas monoclonal antibody induces fibroblast\u2010like synoviocyte apoptosis in haemophilic arthropathy: potential therapeutic implications"],"prefix":"10.1111","volume":"20","author":[{"given":"E.","family":"Romano","sequence":"first","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Manetti","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Melchiorre","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F.","family":"Milia","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bellando\u2010Randone","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Institute of Medical Science Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Innocenti","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Carulli","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Linari","sequence":"additional","affiliation":[{"name":"Regional Reference Center for Inherited Coagulopathies Azienda Ospedaliero\u2010Universitaria Careggi University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Morfini","sequence":"additional","affiliation":[{"name":"Regional Reference Center for Inherited Coagulopathies Azienda Ospedaliero\u2010Universitaria Careggi University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ibba\u2010Manneschi","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Matucci\u2010Cerinic","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Guiducci","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine Division of Rheumatology Department of Experimental and Clinical Medicine Azienda Ospedaliero\u2010Universitaria Careggi, and DENOthe Centre University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07386.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2005.11.026"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02669.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.1999.00608.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01268.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02835.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00648.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199801)41:1<1::AID-ART1>3.0.CO;2-V"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200005)43:5<1106::AID-ANR21>3.0.CO;2-F"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118789"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-221"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120370"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35037710"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402060"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.10964"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2050"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00859.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380405"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00701.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00037-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01870.x"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12304","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T17:28:07Z","timestamp":1695490087000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,20]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1111\/hae.12304"],"URL":"https:\/\/doi.org\/10.1111\/hae.12304","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,20]]}}}