{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:26:30Z","timestamp":1771046790883,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T00:00:00Z","timestamp":1475625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR056228"],"award-info":[{"award-number":["R01 AR056228"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Joint haemorrhage is the principal clinical manifestation of haemophilia frequently leading to advanced arthropathy and arthrofibrosis, resulting in severe disability. The degree and prevalence of arthrofibrosis in hemophilic arthropathy is more severe than in other forms of arthropathy. Expression of connective tissue growth factor (<jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>) has been linked to many fibrotic diseases, but has not been studied in the context of haemophilic arthropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We aim to compare synovial tissues histologically from haemophilia and osteoarthritis patients with advanced arthropathy in order to compare expression of proteins that are possibly aetiologic in the development of arthrofibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human synovial tissues were obtained from 10 haemophilia and 10 osteoarthritis patients undergoing joint surgery and processed for histology and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All samples from haemophilia patients had synovitis with hypertrophy and hyperplasia of synovial villi. Histologically, synovial tissues contained hyperplastic villi with increased cellularity and abundant haemosiderin\u2010 and ferritin\u2010pigmented macrophage\u2010like cells (<jats:styled-content style=\"fixed-case\">HMC<\/jats:styled-content>s), with a perivascular localization in the sub\u2010surface layer. <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> staining was observed in the surface layer and sub\u2010surface layer in all haemophilia patients, exclusively co\u2010localizing with <jats:styled-content style=\"fixed-case\">HMC<\/jats:styled-content>s. Quantification showed that the extent of <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>\u2010positive areas was correlated with the degree of detection of <jats:styled-content style=\"fixed-case\">HMC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> was not observed in any of the samples from osteoarthritis patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using histological analysis, we showed that <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> expression is elevated in haemophilia patients with arthrofibrosis and absent in patients with osteoarthritis. Additionally, we found that <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> is always associated with haemosiderin\u2010pigmented macrophage\u2010like cells, which suggests that <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> is produced by synovial A cells following the uptake of blood breakdown products.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13049","type":"journal-article","created":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T17:43:09Z","timestamp":1476294189000},"source":"Crossref","is-referenced-by-count":11,"title":["Connective tissue growth factor (<scp>CTGF<\/scp>\/<scp>CCN<\/scp>2) in haemophilic arthropathy and arthrofibrosis: a histological analysis"],"prefix":"10.1111","volume":"22","author":[{"given":"J.","family":"Jiang","sequence":"first","affiliation":[{"name":"Hemophilia Treatment Center at Orthopaedic Institute for Children Los Angeles CA USA"},{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. L.","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Khalique","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. M.","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. M.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"J. V.","family":"Luck","sequence":"additional","affiliation":[{"name":"Hemophilia Treatment Center at Orthopaedic Institute for Children Los Angeles CA USA"},{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at University of California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200711000-00007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00003086-198706000-00014","article-title":"Joint contractures in the hemophilias","volume":"219","author":"Atkins RM","year":"1987","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1997.130135000.x"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"Chronic hemophilic synovitis: the role of radiosynovectomy. Treatment of hemophilia","volume":"33","author":"Silva M","year":"2004","journal-title":"World Fed Hemophilia"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02308.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.45.1.21"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200501000-00012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200407000-00004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03270"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3599"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140264"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10206"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/2000-1967-223"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/BLO.0b013e3180312c01"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-004-0742-x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2010.11.010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.50.5.311"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4457"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.12.014"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000162173.27682.7b"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der476"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-014-3023-0"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03742.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21588"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.orthres.2003.08.012"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22385"},{"key":"e_1_2_8_29_1","first-page":"301","article-title":"Fibroblasts and myofibroblasts in wound healing","volume":"7","author":"Darby IA","year":"2014","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3217com"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0699com"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-219378"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.145"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200003000-00012"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100150316"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jse.2006.01.002"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-4-4"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199910)181:1<153::AID-JCP16>3.0.CO;2-K"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010149200"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.2302\/kjm.53.74"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.9.2632"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2008.07.122"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01493.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.11.041"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13049","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T20:25:57Z","timestamp":1695500757000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.13049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,5]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1111\/hae.13049"],"URL":"https:\/\/doi.org\/10.1111\/hae.13049","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,5]]}}}