{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:03:22Z","timestamp":1792782202003,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007949","name":"Swedish Rheumatism Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kock Foundation"},{"name":"King Gustaf V's 80-Year Anniversary Foundation"},{"DOI":"10.13039\/501100004817","name":"Medical Faculty of Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004817","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009780","name":"Region Sk\u00e5ne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u00d6sterlunds Foundation"},{"DOI":"10.13039\/501100003173","name":"Crafoord Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003173","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Thelma Zoegas Fund"},{"name":"Stig and Ragna Gorthon Research Foundation"},{"DOI":"10.13039\/501100005350","name":"Swedish National Centre for Research in Sports","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005350","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tore Nilsson Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C\u2010terminal crosslinking telopeptide of type II collagen (CTX\u2010II) and N\u2010terminal crosslinking telopeptide of type I collagen (NTX\u2010I) in urine after acute anterior cruciate ligament (ACL) rupture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Synovial fluid, serum, and urine were collected from 121 adults on 6 occasions over 5 years after acute ACL injury. Reference samples were obtained from subjects without knee injury. Concentrations of interleukin\u20106 (IL\u20106), IL\u20108, IL\u201010, interferon\u2010\u03b3 (IFN\u03b3), tumor necrosis factor (TNF), aggrecan ARGS neoepitope, CTX\u2010II, and NTX\u2010I were measured by enzyme\u2010linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Shortly after ACL injury, cytokine concentrations in synovial fluid were elevated 6\u2010fold (TNF) to 1,050\u2010fold (IL\u20106) compared to reference levels, while concentrations of aggrecan ARGS neoepitope in synovial fluid and serum and CTX\u2010II in urine were elevated 1.4\u2010fold to 8\u2010fold. Thereafter, concentrations of cytokines and aggrecan ARGS neoepitope in synovial fluid decreased with different half\u2010lives (in years: IL\u20106 0.9, IL\u20108 2.2, IL\u201010 2.3, IFN\u03b3 3.1, TNF 3.6, aggrecan ARGS neoepitope 4.0). After 5 years, the TNF concentration in synovial fluid remained higher than the reference level. There was a correlation between the concentrations of aggrecan ARGS neoepitope in synovial fluid and serum (r\n                      <jats:sub>s<\/jats:sub>\n                      \u2009=\u20090.36). Concentrations of aggrecan ARGS neoepitope in synovial fluid and of CTX\u2010II and NTX\u2010I in urine were correlated with concentrations of cytokines in synovial fluid (r\n                      <jats:sub>s<\/jats:sub>\n                      \u2009=\u20090.41\u20130.49 and r\n                      <jats:sub>s<\/jats:sub>\n                      \u2009=\u20090.21\u20130.31, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Acute ACL injury induced highly increased levels of inflammatory cytokines in the joint, and these were associated with proteolysis of aggrecan and type II collagen. Cytokine levels remained increased up to 5 years after injury, indicative of extended local inflammation in the joint.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39146","type":"journal-article","created":{"date-parts":[[2015,4,24]],"date-time":"2015-04-24T10:47:28Z","timestamp":1429872448000},"page":"1816-1825","source":"Crossref","is-referenced-by-count":108,"title":["Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C\u2010Terminal Crosslinking Telopeptide of Type II Collagen and N\u2010Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligament Rupture: An Exploratory Analysis in the Knee Anterior Cruciate Ligament, Nonsurgical Versus Surgical Treatment Trial"],"prefix":"10.1002","volume":"67","author":[{"given":"Andr\u00e9","family":"Struglics","sequence":"first","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Larsson","sequence":"additional","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Kumahashi","sequence":"additional","affiliation":[{"name":"Lund University, Lund, Sweden, and Shimane University School of Medicine Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Frobell","sequence":"additional","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Stefan","family":"Lohmander","sequence":"additional","affiliation":[{"name":"Lund University, Lund, Sweden, and University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546507307396"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115742"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360207"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11326"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780321113"},{"key":"e_1_2_7_8_1","first-page":"1362","article-title":"Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury","volume":"20","author":"Lohmander LS","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/036354659702500605"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199904)42:3<534::AID-ANR19>3.0.CO;2-J"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0160(02)00083-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23495"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2735"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.05.006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.07.021"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/33.12.1107"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.02.001"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.6.619"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20332"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.042895"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3246"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.07.014"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.08.019"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907797"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f232"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.12.010"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.01.012"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-005-0023-5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22208"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.04.002"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37900"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054633"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(00)00093-7"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2009.07.006"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800181-MCP200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201177"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.4.332"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(95)00243-X"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652309788921044"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.46.7.527"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3555"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2009.12.018"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2005.08.034"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546514524924"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24800"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.12.009"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.09.015"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21359"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947603513487457"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38881"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.05.014"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39146","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39146","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:29:52Z","timestamp":1759922992000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,26]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1002\/art.39146"],"URL":"https:\/\/doi.org\/10.1002\/art.39146","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,26]]}}}