{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:14:22Z","timestamp":1790100862523,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T00:00:00Z","timestamp":1437350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction and aim<\/jats:title>\n                    <jats:p>\n                      Joint bleeding results in blood\u2010induced arthropathy. We investigate whether a joint bleed alters protease\u2010activated receptor (\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      ) expression, and whether treatment with small interfering\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      (siRNA) targeted against\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 attenuates synovitis and cartilage damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Protease\u2010activated receptor expression was evaluated upon a joint bleed in haemophilic mice and in humans. In addition, mice with a joint bleed were randomized between treatment with\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 siRNA or control and evaluated for the presence of synovitis and cartilage damage. Also, human cartilage was transfected with\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 siRNA or control, and evaluated for plasmin\u2010induced cartilage damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following a joint bleed, we observed an increase in synovial\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1, \u20102 and \u20104 expression, and an increase in chondrocyte\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      2 and \u20103 expression in mice (all\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Also an increase in synovial\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1 and chondrocyte\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      4 expression in patients was observed (both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Treatment of a joint bleed in haemophilic mice with\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 siRNA attenuates synovitis and cartilage damage (both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). Treatment of human cartilage tissue explants with\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 siRNA reduced plasmin\u2010induced cartilage damage (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that synovial and chondrocyte\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      expression is altered upon a joint bleed, and that treatment with\n                      <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>\n                      1\u20134 siRNA attenuates synovitis and plasmin\u2010induced cartilage damage.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.12770","type":"journal-article","created":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T05:23:14Z","timestamp":1437369794000},"page":"152-159","source":"Crossref","is-referenced-by-count":9,"title":["Silencing of protease\u2010activated receptors attenuates synovitis and cartilage damage following a joint bleed in haemophilic mice"],"prefix":"10.1111","volume":"22","author":[{"given":"L.","family":"Nieuwenhuizen","sequence":"first","affiliation":[{"name":"Rheumatology and Clinical Immunology University Medical Center Utrecht The Netherlands"},{"name":"Hematology and Van Creveldkliniek University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E. G.","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Hematology and Van Creveldkliniek University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Coeleveld","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. C.","family":"Mastbergen","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. M.","family":"Schiffelers","sequence":"additional","affiliation":[{"name":"Clinical Chemistry and Hematology University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Roosendaal","sequence":"additional","affiliation":[{"name":"Hematology and Van Creveldkliniek University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. H.","family":"Biesma","sequence":"additional","affiliation":[{"name":"Hematology and Van Creveldkliniek University Medical Center Utrecht The Netherlands"},{"name":"Internal Medicine Sint Antonius Ziekenhuis Nieuwegein The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. P. J. 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