{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:02Z","timestamp":1791400922649,"version":"4.3.3"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,25]],"date-time":"2017-06-25T00:00:00Z","timestamp":1498348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy\u2014a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin\u2014OPG; receptor activator of nuclear factor \u03baB\u2014RANK; RANK ligand\u2014RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.<\/jats:p>","DOI":"10.3390\/jcm6070063","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T02:58:05Z","timestamp":1498532285000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Pathophysiology of Hemophilic Arthropathy"],"prefix":"10.3390","volume":"6","author":[{"given":"Daniela","family":"Melchiorre","sequence":"first","affiliation":[{"name":"Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Department of Geriatric Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-8480","authenticated-orcid":false,"given":"Mirko","family":"Manetti","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Matucci-Cerinic","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Department of Geriatric Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/S0140-6736(03)13405-8","article-title":"Haemophilias A and B","volume":"361","author":"Pasi","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S166","DOI":"10.1007\/PL00014347","article-title":"When are children diagnosed as having severe haemophilia and when do they start to bleed? 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