{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:51:08Z","timestamp":1760043068531},"reference-count":50,"publisher":"American Veterinary Medical Association (AVMA)","issue":"10","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To identify chondroprotective factors as potential disease-modifying osteoarthritis treatments using an unbiased, bottom-up proteomics approach.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>SAMPLES<\/jats:title>\n<jats:p>Paired equine cartilage explants and synovial membrane were collected postmortem from 4 horses with no history of lameness and grossly normal joints at necropsy.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>Six groups were established: cartilage, synoviocytes, and cartilage + synoviocytes (coculture), all with or without interleukin (IL)-1\u03b2. The catabolic effect of IL-1\u03b2 was verified by glycosaminoglycan (GAG) released from cartilage into media by 1,9-dimethyl-methylene blue assay and cartilage toluidine blue histochemistry. Conditioned media from cocultures with or with IL-1\u03b2 were submitted for bottom-up proteomic analysis. Synoviocyte gene expression was evaluated using reverse transcription\u2013quantitative PCR (RT-qPCR) for proteins of interest identified in the proteomics scan.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>GAG content was retained in cartilage when in cocultures treated with IL-1\u03b2. Fourteen proteins of interest were selected from the proteomic analysis. From these 14 proteins, metalloproteinase inhibitor 3 precursor (TIMP3), tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), insulin-like growth factor-binding protein 2 (IGFBP2), and alpha-2 macroglobulin (A2M) were selected for synoviocyte gene expression analysis by RT-qPCR. Gene expression of <jats:italic>TIMP3<\/jats:italic> (<jats:italic>P<\/jats:italic> = .02) and <jats:italic>TNFRSF11B<\/jats:italic> (<jats:italic>P<\/jats:italic> = .04) were significantly increased in synoviocytes from cocultures treated with IL-1\u03b2 compared to controls. Contrary to expectations based on protein expression, <jats:italic>IGFBP2<\/jats:italic> gene expression (<jats:italic>P<\/jats:italic> = .04) was significantly decreased in IL-1\u03b2-stimulated coculture synoviocytes compared to control coculture synoviocytes. <jats:italic>A2M<\/jats:italic> gene expression in synoviocytes was not different between coculture groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>The secretome from synoviocytes could provide a milieu of bioactive factors to restore joint homeostasis in osteoarthritis.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.22.05.0082","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T19:39:32Z","timestamp":1660851572000},"source":"Crossref","is-referenced-by-count":3,"title":["Synovium secretome as a disease-modifying treatment for equine osteoarthritis"],"prefix":"10.2460","volume":"83","author":[{"given":"Santiago Mejia","family":"Hernandez","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila","family":"Begum","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Fu","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Facility, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Facility, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Fortier","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Cornell University, Ithaca, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"7","key":"B1","series-title":"Nat Rev Rheumatol","first-page":"412","article-title":"Ageing and the pathogenesis of osteoarthritis","volume":"12","year":"2016","unstructured":"Loeser RF, Collins JA, Diekman BO. 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