{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:24:38Z","timestamp":1790220278511,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Haemophiliac arthritis (HA) is caused by spontaneous intra\u2010articular hemorrhage and repeated intra\u2010articular hematomas, leading to iron overload, which, in turn, induces M1 macrophage polarisation and inflammatory cytokine secretion, resulting in synovitis. Here, we explored the mechanism by which iron overload in HA induces the polarisation of M1 macrophages, providing a new approach for the treatment of HA synovitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The synovium from the knee joints of normal amputees and patients with HA was collected. Pathological changes in the synovial tissues were analysed using hematoxylin and eosin staining. Iron tissue deposition was evaluated using the iron assay kit and Prussia Blue staining, while macrophage phenotype was determined using immunofluorescence. The levels of pro\u2010inflammatory cytokines and p53 acetylation were determine using western blotting. An in vitro iron overload model was established by inducing THP\u20101 macrophages with ferric ammonium citrate, and the involvement of acetylated p53 in M1 macrophage polarisation was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to control samples, the iron content in the synovium of patients with HA was significantly increased. The protein levels of M1 macrophage markers, pro\u2010inflammatory cytokines, and acetylated p53, were also significantly elevated in the synovial tissues of patients with HA. Similar results were observed in the in vitro iron overload model. Furthermore, the inhibition of p53 acetylation in vitro reversed these iron overload\u2010induced effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with HA, iron overload induced synovial p53 acetylation, leading to macrophage polarisation toward the M1 phenotype and increased inflammatory cytokine secretion, resulting in synovitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Synovial iron overload is associated with changes in P53 acetylation in hemophiliac arthritis (HA).\n<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Acetylated p53, a known regulator of macrophage polarization, is highly expressed in HA synovium, suggesting a potential role in M1 polarization.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HA synovial macrophages predominantly polarize into the pro\u2010inflammatory M1 phenotype, secreting elevated levels of pro\u2010inflammatory cytokines.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14905","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T23:55:29Z","timestamp":1701993329000},"page":"195-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Iron overload causes macrophages to produce a pro\u2010inflammatory phenotype in the synovium of hemophiliac arthritis via the acetyl\u2010p53 pathway"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4874-5265","authenticated-orcid":false,"given":"Nanyu","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics the Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics the Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics the Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qigang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Ma Anshan People's Hospital  Ma Anshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-8782","authenticated-orcid":false,"given":"Liujie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Fourth Hospital of Wuhan  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics the Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-2524","authenticated-orcid":false,"given":"Yunfeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics the Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2002.1.1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2005.11.026"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01087.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02127.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02588.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13449"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12208"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01732.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02669.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1676796"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.11.032"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_11_14_1","first-page":"323","article-title":"[Pathology 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