{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:24Z","timestamp":1747185144018,"version":"3.40.5"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Novo Nordisk A\/S"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Haemophilic animal models are used to study blood\u2010induced cartilage damage, but quantitative and sensitive outcome measures are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood\u2010induced joint damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:sup>35<\/jats:sup>Sulphate incorporation (<jats:sup>35<\/jats:sup>SO<jats:sub>4<\/jats:sub><jats:sup>2\u2212<\/jats:sup> assay) was applied to tibial and patellar cartilage of wild\u2010type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4\u2010day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII\u2010deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro\u2010CT). Four\u2010 and 16\u2010day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the <jats:sup>35<\/jats:sup>SO<jats:sub>4<\/jats:sub><jats:sup>2\u2212<\/jats:sup> assay, with the contralateral knee as control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood\u2010exposed knee, tibial and patellar PSR was inhibited 4 and 16\u00a0days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood\u2010exposed knee.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the <jats:sup>35<\/jats:sup>SO<jats:sub>4<\/jats:sub><jats:sup>2\u2212<\/jats:sup> assay in a haemophilic rat model, establishing this assay as a novel method to study blood\u2010induced cartilage damage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13969","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T13:25:43Z","timestamp":1585142743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteoglycan synthesis rate as a novel method to measure blood\u2010induced cartilage degeneration in non\u2010haemophilic and haemophilic rats"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8464-4775","authenticated-orcid":false,"given":"Astrid E.","family":"Pulles","sequence":"first","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center (UMC) Utrecht Utrecht University Utrecht The Netherlands"},{"name":"Van Creveldkliniek UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6701-2087","authenticated-orcid":false,"given":"K\u00e5re K.","family":"V\u00f8ls","sequence":"additional","affiliation":[{"name":"Global Drug Discovery Novo Nordisk A\/S Maaloev Denmark"},{"name":"Veterinary and Animal Sciences University of Copenhagen Frederiksberg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine R.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Veterinary and Animal Sciences University of Copenhagen Frederiksberg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Coeleveld","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center (UMC) Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel K.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Veterinary and Animal Sciences University of Copenhagen Frederiksberg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-5524","authenticated-orcid":false,"given":"Lize F. D.","family":"van Vulpen","sequence":"additional","affiliation":[{"name":"Van Creveldkliniek UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maj","family":"Petersen","sequence":"additional","affiliation":[{"name":"Global Drug Discovery Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon C.","family":"Mastbergen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center (UMC) Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirstine","family":"Roepstorff","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S Ballerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-6033","authenticated-orcid":false,"given":"Roger E. G.","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Van Creveldkliniek UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads","family":"Kjelgaard\u2010Hansen","sequence":"additional","affiliation":[{"name":"Veterinary Clinical Sciences University of Copenhagen Frederiksberg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris P. J. G.","family":"Lafeber","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center (UMC) Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02909.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2008.69.8.30743"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.knee.2009.06.008"},{"issue":"2","key":"e_1_2_9_5_1","first-page":"339","article-title":"Blood\u2010induced joint damage: longterm effects in vitro and in vivo","volume":"30","author":"Hooiveld M","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1641755"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22304"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63889-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199905)42:5<1033::AID-ANR24>3.0.CO;2-#"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key186"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.11.032"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13449"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.09.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13554"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13328"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13672"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008209309016834"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100120204"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2003.11.008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100110404"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.76B3.8175856"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541171"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199905)42:5<1025::AID-ANR23>3.0.CO;2-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02608.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13080"},{"issue":"7","key":"e_1_2_9_26_1","first-page":"1350","article-title":"Cartilage damage as a result of hemarthrosis in a human in vitro model","volume":"24","author":"Roosendaal G","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_9_27_1","first-page":"11","article-title":"Animal models of osteoarthritis\u2014Why choose a larger model?","volume":"4","author":"Mastbergen SC","year":"2009","journal-title":"US Musculoskelet Rev"},{"issue":"7","key":"e_1_2_9_28_1","first-page":"1740","article-title":"Articular cartilage is more susceptible to blood induced damage at young than at old age","volume":"27","author":"Roosendaal G","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10769"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24133"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-734053"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.09.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200002)43:2<298::AID-ANR9>3.0.CO;2-G"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01527.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/1056-8719(94)90046-9"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12635"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH17-03-0149"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar121"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kei156"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00512-O"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-820571"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13969","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13969","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.13969","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:01:17Z","timestamp":1693918877000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.13969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/hae.13969"],"URL":"https:\/\/doi.org\/10.1111\/hae.13969","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"type":"print","value":"1351-8216"},{"type":"electronic","value":"1365-2516"}],"subject":[],"published":{"date-parts":[[2020,3,25]]},"assertion":[{"value":"2019-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}