{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:38:52Z","timestamp":1793057932582,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Grant-in-Aid for Scientific Research (C)"],"award-info":[{"award-number":["Grant-in-Aid for Scientific Research (C)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004721","name":"The University of Tokyo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004721","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Bone Miner Metab"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.<\/jats:p>","DOI":"10.1007\/s00774-024-01520-8","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T07:01:41Z","timestamp":1718002901000},"page":"455-462","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-5656","authenticated-orcid":false,"given":"Asuka","family":"Terashima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Omata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakae","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-3930","authenticated-orcid":false,"given":"Taku","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"1520_CR1","doi-asserted-by":"publisher","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","volume":"4","author":"JS Smolen","year":"2018","unstructured":"Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K (2018) Rheumatoid arthritis. Nat Rev Dis Primers 4:18001. https:\/\/doi.org\/10.1038\/nrdp.2018.1","journal-title":"Nat Rev Dis Primers"},{"key":"1520_CR2","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1111\/j.1538-7836.2010.03962.x","volume":"8","author":"L Valentino","year":"2010","unstructured":"Valentino L (2010) Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. J Thromb Haemost 8:1895\u20131902","journal-title":"J Thromb Haemost"},{"key":"1520_CR3","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1136\/annrheumdis-2019-215920","volume":"78","author":"S Safiri","year":"2019","unstructured":"Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, Almasi-Hashiani A, Ashrafi-Asgarabad A, Moradi-Lakeh M, Qorbani M, Collins G, Woolf AD, March L, Cross M (2019) Global, regional and national burden of rheumatoid arthritis 1990\u20132017: a systematic analysis of the global burden of disease study 2017. Ann Rheum Dis 78:1463\u20131471. https:\/\/doi.org\/10.1136\/annrheumdis-2019-215920","journal-title":"Ann Rheum Dis"},{"key":"1520_CR4","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1111\/1756-185X.13974","volume":"23","author":"A Nakajima","year":"2020","unstructured":"Nakajima A, Sakai R, Inoue E, Harigai M (2020) Prevalence of patients with rheumatoid arthritis and age-stratified trends in clinical characteristics and treatment, based on the national database of health insurance claims and specific health checkups of Japan. Int J Rheum Dis 23:1676\u20131684","journal-title":"Int J Rheum Dis"},{"key":"1520_CR5","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1080\/14397595.2019.1682776","volume":"30","author":"M Kojima","year":"2020","unstructured":"Kojima M, Nakayama T, Tsutani K, Igarashi A, Kojima T, Suzuki S, Miyasaka N, Yamanaka H (2020) Epidemiological characteristics of rheumatoid arthritis in Japan: prevalence estimates using a nationwide population-based questionnaire survey. Mod Rheumatol 30:941\u2013947. https:\/\/doi.org\/10.1080\/14397595.2019.1682776","journal-title":"Mod Rheumatol"},{"key":"1520_CR6","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1182\/blood-2014-07-586347","volume":"124","author":"T Calvez","year":"2014","unstructured":"Calvez T, Chambost H, Claeyssens-Donadel S, d\u2019Oiron R, Goulet V, Guillet B, H\u00e9ritier V, Milien V, Rothschild C, Roussel-Robert V, Vinciguerra C, Goudemand J, Network F (2014) Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood 124:3398\u20133408. https:\/\/doi.org\/10.1182\/blood-2014-07-586347","journal-title":"Blood"},{"key":"1520_CR7","unstructured":"Nationwide Survey on Coagulation Disorders 2022 (2022) Japan Foundation for AIDS Prevention"},{"key":"1520_CR8","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1055\/s-0031-1297164","volume":"37","author":"R Kulkarni","year":"2011","unstructured":"Kulkarni R, Soucie JM (2011) Pediatric hemophilia: a review. Semin Thromb Hemost 37:737\u2013744. https:\/\/doi.org\/10.1055\/s-0031-1297164","journal-title":"Semin Thromb Hemost"},{"key":"1520_CR9","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1182\/blood-2016-02-683169","volume":"129","author":"Manco-Johnson MJ, Soucie JM, Gill JC, Joint Outcomes Committee of the Universal Data Collection USHTCN","year":"2017","unstructured":"Manco-Johnson MJ, Soucie JM, Gill JC, Joint Outcomes Committee of the Universal Data Collection USHTCN (2017) Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project. Blood 129:2368\u20132374. https:\/\/doi.org\/10.1182\/blood-2016-02-683169","journal-title":"Blood"},{"key":"1520_CR10","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/ng.582","volume":"42","author":"EA Stahl","year":"2010","unstructured":"Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, Li Y, Kurreeman FA, Zhernakova A, Hinks A (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42:508\u2013514","journal-title":"Nat Genet"},{"key":"1520_CR11","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/ng.2231","volume":"44","author":"Y Okada","year":"2012","unstructured":"Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N (2012) Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet 44:511\u2013516","journal-title":"Nat Genet"},{"key":"1520_CR12","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature12873","volume":"506","author":"Y Okada","year":"2014","unstructured":"Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506:376\u2013381","journal-title":"Nature"},{"key":"1520_CR13","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1038\/ng.2462","volume":"44","author":"S Eyre","year":"2012","unstructured":"Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K (2012) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet 44:1336\u20131340","journal-title":"Nat Genet"},{"key":"1520_CR14","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1086\/422827","volume":"75","author":"AB Begovich","year":"2004","unstructured":"Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330\u2013337","journal-title":"Am J Hum Genet"},{"key":"1520_CR15","first-page":"708","volume":"28","author":"LM Elsby","year":"2010","unstructured":"Elsby LM, Orozco G, Denton J, Worthington J, Ray DW, Donn RP (2010) Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis. Clin Exp Rheumatol 28:708","journal-title":"Clin Exp Rheumatol"},{"key":"1520_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar2650","volume":"11","author":"R Dieguez-Gonzalez","year":"2009","unstructured":"Dieguez-Gonzalez R, Calaza M, Perez-Pampin E, Balsa A, Blanco FJ, Ca\u00f1ete JD, Caliz R, Carre\u00f1o L, de la Serna AR, Fernandez-Gutierrez B (2009) Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-\u03baB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility. Arthritis Res Ther 11:1\u20138","journal-title":"Arthritis Res Ther"},{"key":"1520_CR17","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/ng.874","volume":"43","author":"M Matmati","year":"2011","unstructured":"Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, Geboes L, Louagie E, Guire CM, Vereecke L (2011) A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet 43:908\u2013912","journal-title":"Nat Genet"},{"key":"1520_CR18","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/ng.583","volume":"42","author":"Y Kochi","year":"2010","unstructured":"Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T (2010) A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet 42:515\u2013519","journal-title":"Nat Genet"},{"key":"1520_CR19","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1084\/jem.20071397","volume":"204","author":"K Hirota","year":"2007","unstructured":"Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, Yamaguchi T, Nomura T, Ito H, Nakamura T (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204:2803\u20132812","journal-title":"J Exp Med"},{"key":"1520_CR20","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1136\/ard.2007.085704","volume":"68","author":"K Shimane","year":"2009","unstructured":"Shimane K, Kochi Y, Yamada R, Okada Y, Suzuki A, Miyatake A, Kubo M, Nakamura Y, Yamamoto K (2009) A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population. Ann Rheum Dis 68:377\u2013383","journal-title":"Ann Rheum Dis"},{"key":"1520_CR21","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1080\/03009740802256327","volume":"37","author":"A Maalej","year":"2008","unstructured":"Maalej A, Hamad MB, Rebai A, Teixeira VH, Bahloul Z, Marzouk S, Farid NR, Ayadi H, Corn\u00e9lis F, Petit-Teixeira E (2008) Association of IRF5 gene polymorphisms with rheumatoid arthritis in a Tunisian population. Scand J Rheumatol 37:414\u2013418","journal-title":"Scand J Rheumatol"},{"key":"1520_CR22","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.3324\/haematol.2019.221093","volume":"104","author":"G Castaman","year":"2019","unstructured":"Castaman G, Matino D (2019) Hemophilia A and B: molecular and clinical similarities and differences. Haematologica 104:1702\u20131709. https:\/\/doi.org\/10.3324\/haematol.2019.221093","journal-title":"Haematologica"},{"key":"1520_CR23","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.1182\/blood-2006-05-024711","volume":"108","author":"Astermark J, Oldenburg J, Carlson J, Pavlova A, Kavakli K, Berntorp E, Lefvert A-K, Group MS","year":"2006","unstructured":"Astermark J, Oldenburg J, Carlson J, Pavlova A, Kavakli K, Berntorp E, Lefvert A-K, Group MS (2006) Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A. Blood 108:3739\u20133745","journal-title":"Blood"},{"key":"1520_CR24","doi-asserted-by":"publisher","first-page":"589","DOI":"10.2147\/JBM.S343924","volume":"13","author":"R Cuesta-Barriuso","year":"2022","unstructured":"Cuesta-Barriuso R, Donoso-\u00dabeda E, Mero\u00f1o-Gallut J, Ucero-Lozano R, P\u00e9rez-Llanes R (2022) Hemophilic arthropathy: barriers to early diagnosis and management. J Blood Med 13:589\u2013601. https:\/\/doi.org\/10.2147\/JBM.S343924","journal-title":"J Blood Med"},{"key":"1520_CR25","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12669","author":"A Torres-Ortu\u00f1o","year":"2018","unstructured":"Torres-Ortu\u00f1o A, Cuesta-Barriuso R, Nieto-Munuera J, Galindo-Pi\u00f1ana P, L\u00f3pez-Pina JA (2018) The behaviour and perception of illness: modulating variables of adherence in patients with haemophilia. Vox Sang. https:\/\/doi.org\/10.1111\/vox.12669","journal-title":"Vox Sang"},{"key":"1520_CR26","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s10787-021-00800-3","volume":"29","author":"SSA Ibrahim","year":"2021","unstructured":"Ibrahim SSA, Huttunen KM (2021) Orchestrated modulation of rheumatoid arthritis via crosstalking intracellular signaling pathways. Inflammopharmacology 29:965\u2013974. https:\/\/doi.org\/10.1007\/s10787-021-00800-3","journal-title":"Inflammopharmacology"},{"key":"1520_CR27","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1152\/physrev.00036.2016","volume":"97","author":"K Okamoto","year":"2017","unstructured":"Okamoto K, Nakashima T, Shinohara M, Negishi-Koga T, Komatsu N, Terashima A, Sawa S, Nitta T, Takayanagi H (2017) Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol Rev 97:1295\u20131349. https:\/\/doi.org\/10.1152\/physrev.00036.2016","journal-title":"Physiol Rev"},{"key":"1520_CR28","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1080\/1744666X.2017.1295850","volume":"13","author":"M Narazaki","year":"2017","unstructured":"Narazaki M, Tanaka T, Kishimoto T (2017) The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol 13:535\u2013551","journal-title":"Expert Rev Clin Immunol"},{"key":"1520_CR29","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1093\/rheumatology\/38.3.202","volume":"38","author":"G Steiner","year":"1999","unstructured":"Steiner G, Tohidast-Akrad M, Witzmann G, Vesely M, Studnicka-Benke A, Gal A, Kunaver M, Zenz P, Smolen J (1999) Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology (Oxford) 38:202\u2013213","journal-title":"Rheumatology (Oxford)"},{"key":"1520_CR30","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.4049\/jimmunol.157.7.3178","volume":"157","author":"L Mori","year":"1996","unstructured":"Mori L, Iselin S, De Libero G, Lesslauer W (1996) Attenuation of collagen-induced arthritis in 55-kDa TNF receptor type 1 (TNFR1)-IgG1-treated and TNFR1-deficient mice. J Immunol (Baltimore, Md: 1950) 157:3178\u20133182","journal-title":"J Immunol (Baltimore, Md: 1950)"},{"key":"1520_CR31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1080\/14397595.2017.1369491","volume":"28","author":"S Tanaka","year":"2018","unstructured":"Tanaka S, Tanaka Y, Ishiguro N, Yamanaka H, Takeuchi T (2018) RANKL: a therapeutic target for bone destruction in rheumatoid arthritis. Mod Rheumatol 28:9\u201316","journal-title":"Mod Rheumatol"},{"key":"1520_CR32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.1365-2516.2006.01268.x","volume":"12","author":"G Roosendaal","year":"2006","unstructured":"Roosendaal G, Lafeber FP (2006) Pathogenesis of haemophilic arthropathy (in eng). Haemophilia 12:117\u2013121. https:\/\/doi.org\/10.1111\/j.1365-2516.2006.01268.x","journal-title":"Haemophilia"},{"key":"1520_CR33","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1093\/rheumatology\/keg220","volume":"42","author":"MJ Hooiveld","year":"2003","unstructured":"Hooiveld MJ, Roosendaal G, Van Den Berg H, Bijlsma J, Lafeber F (2003) Haemoglobin-derived iron-dependent hydroxyl radical formation in blood-induced joint damage: an in vitro study. Rheumatology 42:784\u2013790","journal-title":"Rheumatology"},{"key":"1520_CR34","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1111\/j.1365-2516.2008.01973.x","volume":"15","author":"K \u00d8vlisen","year":"2009","unstructured":"\u00d8vlisen K, Kristensen AT, Jensen AL, Tranholm M (2009) IL-1, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis. Haemophilia 15:802\u2013810. https:\/\/doi.org\/10.1111\/j.1365-2516.2008.01973.x","journal-title":"Haemophilia"},{"key":"1520_CR35","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri2094","volume":"7","author":"IB McInnes","year":"2007","unstructured":"McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429\u2013442","journal-title":"Nat Rev Immunol"},{"key":"1520_CR36","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1111\/j.1742-4658.2008.06580.x","volume":"275","author":"T Iwamoto","year":"2008","unstructured":"Iwamoto T, Okamoto H, Toyama Y, Momohara S (2008) Molecular aspects of rheumatoid arthritis: chemokines in the joints of patients. FEBS J 275:4448\u20134455","journal-title":"FEBS J"},{"key":"1520_CR37","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1046\/j.1365-2559.1999.00608.x","volume":"34","author":"V Roosendaal","year":"1999","unstructured":"Roosendaal V, Lafeber B (1999) Haemophilic arthropathy resembles degenerative rather than inflammatory joint disease. Histopathology 34:144\u2013153","journal-title":"Histopathology"},{"key":"1520_CR38","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1111\/jth.12176","volume":"11","author":"N Narkbunnam","year":"2013","unstructured":"Narkbunnam N, Sun J, Hu G, Lin F-C, Bateman TA, Mihara M, Monahan PE (2013) IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia. J Thromb Haemost 11:881\u2013893","journal-title":"J Thromb Haemost"},{"key":"1520_CR39","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1002\/JLB.3A0318-108R","volume":"105","author":"P Handa","year":"2019","unstructured":"Handa P, Thomas S, Morgan-Stevenson V, Maliken BD, Gochanour E, Boukhar S, Yeh MM, Kowdley KV (2019) Iron alters macrophage polarization status and leads to steatohepatitis and fibrogenesis. J Leukoc Biol 105:1015\u20131026","journal-title":"J Leukoc Biol"},{"key":"1520_CR40","doi-asserted-by":"publisher","first-page":"4012","DOI":"10.1002\/cam4.1670","volume":"7","author":"Y Zhou","year":"2018","unstructured":"Zhou Y, Que KT, Zhang Z, Yi ZJ, Zhao PX, You Y, Gong JP, Liu ZJ (2018) Iron overloaded polarizes macrophage to proinflammation phenotype through ROS\/acetyl-p53 pathway. Cancer Med 7:4012\u20134022. https:\/\/doi.org\/10.1002\/cam4.1670","journal-title":"Cancer Med"},{"key":"1520_CR41","first-page":"1064","volume":"132","author":"C Haxaire","year":"2018","unstructured":"Haxaire C, Hakobyan N, Pannellini T, Carballo C, McIlwain D, Mak TW, Rodeo S, Acharya S, Li D, Szymonifka J (2018) Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2\/ADAM17\/TNF-\u03b1 pathway. Blood J Am Soc Hematol 132:1064\u20131074","journal-title":"Blood J Am Soc Hematol"},{"key":"1520_CR42","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0968-0160(02)00083-2","volume":"10","author":"K Irie","year":"2003","unstructured":"Irie K, Uchiyama E, Iwaso H (2003) Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee 10:93\u201396","journal-title":"Knee"},{"key":"1520_CR43","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/rheumatology\/ket280","volume":"53","author":"D Melchiorre","year":"2014","unstructured":"Melchiorre D, Morfini M, Linari S, Zignego AL, Innocenti M, Matucci Cerinic M (2014) Anti-TNF-\u03b1 therapy prevents the recurrence of joint bleeding in haemophilia and arthritis. Rheumatology (Oxford) 53:576\u2013578. https:\/\/doi.org\/10.1093\/rheumatology\/ket280","journal-title":"Rheumatology (Oxford)"},{"key":"1520_CR44","first-page":"2239","volume":"126","author":"LF van Vulpen","year":"2015","unstructured":"van Vulpen LF, Schutgens RE, Coeleveld K, Alsema EC, Roosendaal G, Mastbergen SC, Lafeber FP (2015) IL-1\u03b2, in contrast to TNF\u03b1, is pivotal in blood-induced cartilage damage and is a potential target for therapy. Blood J Am Soc Hematol 126:2239\u20132246","journal-title":"Blood J Am Soc Hematol"},{"key":"1520_CR45","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nrc.2016.73","volume":"16","author":"R Kalluri","year":"2016","unstructured":"Kalluri R (2016) The biology and function of fibroblasts in cancer. Nat Rev Cancer 16:582\u2013598. https:\/\/doi.org\/10.1038\/nrc.2016.73","journal-title":"Nat Rev Cancer"},{"key":"1520_CR46","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.4049\/jimmunol.161.7.3340","volume":"161","author":"U Schonbeck","year":"1998","unstructured":"Schonbeck U, Mach F, Libby P (1998) Generation of biologically active IL-1\u03b2 by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1\u03b2 processing. J Immunol 161:3340\u20133346","journal-title":"J Immunol"},{"key":"1520_CR47","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/j.biocel.2007.11.026","volume":"40","author":"G Jenkins","year":"2008","unstructured":"Jenkins G (2008) The role of proteases in transforming growth factor-\u03b2 activation. Int J Biochem Cell Biol 40:1068\u20131078","journal-title":"Int J Biochem Cell Biol"},{"key":"1520_CR48","doi-asserted-by":"publisher","first-page":"5505","DOI":"10.1182\/bloodadvances.2022007028","volume":"6","author":"WW Hauw","year":"2022","unstructured":"Hauw WW, Chia JS, Nandurkar HH, Sashindranath M (2022) The potential role of protease systems in hemophilic arthropathy. Blood Adv 6:5505\u20135515","journal-title":"Blood Adv"},{"key":"1520_CR49","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1093\/rheumatology\/kei025","volume":"44","author":"NJ Peake","year":"2005","unstructured":"Peake NJ, Khawaja K, Myers A, Jones D, Cawston TE, Rowan AD, Foster HE (2005) Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study. Rheumatology (Oxford) 44:1383\u20131389. https:\/\/doi.org\/10.1093\/rheumatology\/kei025","journal-title":"Rheumatology (Oxford)"},{"key":"1520_CR50","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/hae.14443","volume":"28","author":"L Zheng","year":"2022","unstructured":"Zheng L, Luo D, Li J, Ye H, Han Z, Feng R, Zhong Q, Jing J, Yao Y (2022) Pathological changes and expression of lysine oxidases and matrix metalloproteinases -1, -2, and -3 in ligaments of patients with haemophilic arthritis. Haemophilia 28:145\u2013150. https:\/\/doi.org\/10.1111\/hae.14443","journal-title":"Haemophilia"},{"key":"1520_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13075-016-0948-7","volume":"18","author":"K Shiozawa","year":"2016","unstructured":"Shiozawa K, Yamane T, Murata M, Yoshihara R, Tsumiyama K, Imura S, Shiozawa S (2016) MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy. Arthritis Res Ther 18:1\u20139","journal-title":"Arthritis Res Ther"},{"key":"1520_CR52","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1093\/rheumatology\/keg037","volume":"42","author":"M Green","year":"2003","unstructured":"Green M, Gough A, Devlin J, Smith J, Astin P, Taylor D, Emery P (2003) Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology 42:83\u201388","journal-title":"Rheumatology"},{"key":"1520_CR53","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1136\/ard.59.6.455","volume":"59","author":"Y Yoshihara","year":"2000","unstructured":"Yoshihara Y, Nakamura H, Ki O, Yamada H, Hayakawa T, Fujikawa K, Okada Y (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 59:455\u2013461","journal-title":"Ann Rheum Dis"},{"key":"1520_CR54","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1002\/art.1780400806","volume":"40","author":"O Lindy","year":"1997","unstructured":"Lindy O, Konttinen YT, Sorsa T, Ding Y, Santavirta S, Ceponis A, L\u00f3pez-ot\u00edn C (1997) Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthr Rheum: Off J Am Coll Rheumatol 40:1391\u20131399","journal-title":"Arthr Rheum: Off J Am Coll Rheumatol"},{"key":"1520_CR55","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1186\/s12891-020-03795-0","volume":"21","author":"Y Sogi","year":"2020","unstructured":"Sogi Y, Yabe Y, Hagiwara Y, Tsuchiya M, Onoda Y, Sekiguchi T, Itaya N, Yoshida S, Yano T, Suzuki K, Onoki T, Itoi E (2020) Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model. BMC Musculoskelet Disord 21:761. https:\/\/doi.org\/10.1186\/s12891-020-03795-0","journal-title":"BMC Musculoskelet Disord"},{"key":"1520_CR56","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/jth.12101","volume":"11","author":"D Sen","year":"2013","unstructured":"Sen D, Chapla A, Walter N, Daniel V, Srivastava A, Jayandharan GR (2013) Nuclear factor (NF)-\u03baB and its associated pathways are major molecular regulators of blood-induced joint damage in a murine model of hemophilia (in eng). J Thromb Haemost 11:293\u2013306. https:\/\/doi.org\/10.1111\/jth.12101","journal-title":"J Thromb Haemost"},{"key":"1520_CR57","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/72855","volume":"24","author":"K Matsuo","year":"2000","unstructured":"Matsuo K, Owens JM, Tonko M, Elliott C, Chambers TJ, Wagner EF (2000) Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation. Nat Genet 24:184\u2013187","journal-title":"Nat Genet"},{"key":"1520_CR58","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1172\/JCI0215582","volume":"110","author":"K Redlich","year":"2002","unstructured":"Redlich K, Hayer S, Ricci R, David J-P, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G (2002) Osteoclasts are essential for TNF-\u03b1\u2013mediated joint destruction. J Clin Investig 110:1419\u20131427","journal-title":"J Clin Investig"},{"key":"1520_CR59","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1093\/rheumatology\/ken363","volume":"47","author":"M Hashizume","year":"2008","unstructured":"Hashizume M, Hayakawa N, Mihara M (2008) IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-\u03b1 and IL-17. Rheumatology 47:1635\u20131640","journal-title":"Rheumatology"},{"key":"1520_CR60","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.3899\/jrheum.120370","volume":"39","author":"D Melchiorre","year":"2012","unstructured":"Melchiorre D, Milia AF, Linari S, Romano E, Benelli G, Manetti M, Guiducci S, Ceccarelli C, Innocenti M, Carulli C (2012) RANK-RANKL-OPG in hemophilic arthropathy: from clinical and imaging diagnosis to histopathology. J Rheumatol 39:1678\u20131686","journal-title":"J Rheumatol"},{"key":"1520_CR61","doi-asserted-by":"publisher","first-page":"e472","DOI":"10.1111\/hae.12808","volume":"21","author":"S Zhang","year":"2015","unstructured":"Zhang S, Lu C, Ying J, Wang P, Xu T, Chen D, Jin H, Tong P (2015) Inflammatory focal bone destruction in femoral heads with end-stage haemophilic arthropathy: a study on clinic samples with micro-CT and histological analyses. Haemophilia 21:e472\u2013e478. https:\/\/doi.org\/10.1111\/hae.12808","journal-title":"Haemophilia"},{"key":"1520_CR62","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235867","author":"G Adami","year":"2019","unstructured":"Adami G, Fassio A, Rossini M, Caimmi C, Giollo A, Orsolini G, Viapiana O, Gatti D (2019) Osteoporosis in rheumatic diseases. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms20235867","journal-title":"Int J Mol Sci"},{"key":"1520_CR63","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1080\/17474086.2022.2108783","volume":"15","author":"EC Rodriguez-Merchan","year":"2022","unstructured":"Rodriguez-Merchan EC (2022) Osteoporosis in hemophilia: what is its importance in clinical practice? Expert Rev Hematol 15:697\u2013710. https:\/\/doi.org\/10.1080\/17474086.2022.2108783","journal-title":"Expert Rev Hematol"},{"key":"1520_CR64","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1160\/TH13-01-0030","volume":"110","author":"P Anagnostis","year":"2013","unstructured":"Anagnostis P, Vyzantiadis TA, Charizopoulou M, Adamidou F, Karras S, Goulis DG, Karagiannis A, Garipidou V, Vakalopoulou S (2013) The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture. Thromb Haemost 110:257\u2013263. https:\/\/doi.org\/10.1160\/TH13-01-0030","journal-title":"Thromb Haemost"},{"key":"1520_CR65","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1136\/annrheumdis-2015-208052","volume":"75","author":"T Takeuchi","year":"2016","unstructured":"Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T, Okubo N, Genant HK, van der Heijde D (2016) Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (denosumab) in patients with rheumatoId arthritis on methotrexate to validate inhibitory effect on bone erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann Rheum Dis 75:983\u2013990. https:\/\/doi.org\/10.1136\/annrheumdis-2015-208052","journal-title":"Ann Rheum Dis"}],"container-title":["Journal of Bone and Mineral Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-024-01520-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00774-024-01520-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-024-01520-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T05:07:27Z","timestamp":1726808847000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00774-024-01520-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,10]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["1520"],"URL":"https:\/\/doi.org\/10.1007\/s00774-024-01520-8","relation":{},"ISSN":["0914-8779","1435-5604"],"issn-type":[{"value":"0914-8779","type":"print"},{"value":"1435-5604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,10]]},"assertion":[{"value":"13 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}