{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:32:39Z","timestamp":1789662759515,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T00:00:00Z","timestamp":1109894400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. The aim of this study was to investigate the effect of EPO on collagen\u2010induced arthritis (CIA) in the mouse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CIA was induced by intradermal injection of bovine type II collagen (CII) and Freund's complete adjuvant. Starting on day 25, some of the mice with CIA received daily subcutaneous injections of EPO (1,000 units\/kg). Two other groups of mice received sham treatment alone or sham treatment followed by EPO treatment, respectively. Arthritis was assessed clinically, radiologically, and histologically. Cytokine and chemokine levels were measured, and neutrophil infiltration into inflamed joints was quantitated. Immunohistochemistry studies were performed to measure protein nitrosylation. Chondrocyte apoptosis was assessed by TUNEL assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII\u2010challenged mice, and the severity of CIA progressed over a 35\u2010day period, with radiographic evaluation revealing focal resorption of bone. Histopathologic features of CIA included erosion of the cartilage at the joint margins. Treatment with EPO starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26\u201335 and improved histologic status in the joints and paws. The degree of oxidative and nitrosative damage was significantly reduced in EPO\u2010treated mice as indicated by decreased nitrotyrosine formation and poly(ADP\u2010ribose) polymerase activation. Plasma levels of the proinflammatory cytokine tumor necrosis factor \u03b1 were also significantly reduced by EPO treatment. In addition, EPO reduced the levels of apoptosis in chondrocytes in articular cartilage, as indicated by decreased TUNEL staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20875","type":"journal-article","created":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T15:51:33Z","timestamp":1109951493000},"page":"940-950","source":"Crossref","is-referenced-by-count":39,"title":["Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse"],"prefix":"10.1002","volume":"52","author":[{"given":"Salvatore","family":"Cuzzocrea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Mazzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"di Paola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Genovese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimesh S. A.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Britti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"de Majo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille P.","family":"Caputi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Thiemermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,4]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005033221805"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.02.040184.001215"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1990.tb00817.x"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2648569"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/347669a0"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/361079a0"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7682337"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.64.1775"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9748"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4635"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00306-5"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.19.10526"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-24-09733.2001"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200204000-00003"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000080381.76409.B2"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18200"},{"key":"e_1_2_5_18_2","first-page":"351","article-title":"The anemia of chronic disorders","volume":"3","author":"Cartwright GE","year":"1966","journal-title":"Semin Hematol"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103255"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103380"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103500"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200006)30:6<1568::AID-IMMU1568>3.0.CO;2-R"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3867"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00142-7"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.7.3559"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1985.59.6.1978"},{"key":"e_1_2_5_27_2","first-page":"135","article-title":"Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia\/reperfusion injury","volume":"53","author":"Cuzzocrea S","year":"2001","journal-title":"Pharmacol Rev"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M907604199"},{"key":"e_1_2_5_29_2","first-page":"153","article-title":"Non\u2010proteolytic activation of latent human neutrohil collagenase and its role in matrix destruction in periodontal diseases","volume":"11","author":"Sorsa T","year":"1989","journal-title":"Int J Tissue React"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2700459"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2460599"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050501"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(00)01757-3"},{"key":"e_1_2_5_34_2","first-page":"S35","article-title":"A perspective on anti\u2010cytokine and anti\u2010T cell\u2010directed therapies in rheumatoid arthritis","volume":"12","author":"Maini RN","year":"1995","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_5_35_2","first-page":"601","article-title":"Phase I\/II trial of recombinant methionyl human tumor necrosis factor binding protein PEGylated dimer in patients with active refractory rheumatoid arthritis","volume":"27","author":"Moreland LW","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/34923"},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00469-9"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(97)00280-3"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702275"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2659"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13868.x"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702521"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/1071576021000016418"},{"key":"e_1_2_5_45_2","first-page":"357","article-title":"Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants","volume":"55","author":"Akisu M","year":"2001","journal-title":"Acta Med Okayama"},{"key":"e_1_2_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(98)01193-6"},{"key":"e_1_2_5_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01076101"},{"key":"e_1_2_5_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01417-9"},{"key":"e_1_2_5_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000039103.58920.1F"},{"key":"e_1_2_5_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00847.x"},{"key":"e_1_2_5_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.296.5573.1655"},{"key":"e_1_2_5_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.00001276869.21260.9d"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20875","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:01:39Z","timestamp":1697058099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1002\/art.20875"],"URL":"https:\/\/doi.org\/10.1002\/art.20875","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3]]}}}