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We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee\u2010healthy donors. The meniscal body was cut into vertical slices\u00a0and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography\u2013mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed\u2010effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1\u00df increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM)\u2009+\u2009tumor necrosis factor (TNF) and TNF+interleukin\u20106 (IL6)\u2009+\u2009sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.<\/jats:p>","DOI":"10.1002\/jor.25633","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T07:05:21Z","timestamp":1684825521000},"page":"2765-2778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A human meniscus explant model for studying early events in osteoarthritis development by proteomics"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-4314","authenticated-orcid":false,"given":"Martin","family":"Ryd\u00e9n","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Lindblom","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Yifter\u2010Lindgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Turkiewicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Aspberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viveka","family":"Tillgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Englund","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-2937","authenticated-orcid":false,"given":"Patrik","family":"\u00d6nnerfjord","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology Faculty of Medicine Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60802-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34453"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.0c00143"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-020-00122-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-2003-y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-349"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.818542"},{"issue":"2","key":"e_1_2_10_9_1","first-page":"122","article-title":"Human knee synovial fluid cytokines correlated with grade of knee osteoarthritis\u2010\u2010a pilot study","volume":"69","author":"Vangsness CT","year":"2011","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/561459"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-000-0021-y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.11.002"},{"issue":"3","key":"e_1_2_10_13_1","first-page":"1","article-title":"Explant models for meniscus metabolism, injury, repair, and healing","volume":"61","author":"Tarafder S","year":"2019","journal-title":"Connect Tissue Res"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2018.09.016"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(86)90306-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.12.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_10_18_1","unstructured":"LenthRV.2022. emmeans: Estimated Marginal Means aka Least\u2010Squares Means. 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