{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T20:35:38Z","timestamp":1783715738503,"version":"3.55.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The current research was funded by the Bright Sparks program of the University of Veterinary Medicine Vienna, Austria."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0214709","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T17:33:55Z","timestamp":1554226435000},"page":"e0214709","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":77,"title":["Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2415-4496","authenticated-orcid":true,"given":"Eva","family":"Haltmayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Ribitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Gabner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Rosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Gueltekin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Peham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Giese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Dolezal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Egerbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florien","family":"Jenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"issue":"3","key":"ref1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.semarthrit.2014.06.005","article-title":"A reference case for economic evaluations in osteoarthritis: an expert consensus article from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)","volume":"44","author":"M Hiligsmann","year":"2014","journal-title":"Seminars in arthritis and rheumatism"},{"issue":"2","key":"ref2","first-page":"107","article-title":"Articular cartilage and changes in arthritis","volume":"3","author":"LJ Sandell","year":"2001","journal-title":"An introduction: cell biology of osteoarthritis. Arthritis research"},{"issue":"3","key":"ref3","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jcp.21258","article-title":"Osteoarthritis","volume":"213","author":"MB Goldring","year":"2007","journal-title":"Journal of cellular physiology"},{"issue":"933","key":"ref4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1136\/pmj.79.933.377","article-title":"Osteoarthritis","volume":"79","author":"I Haq","year":"2003","journal-title":"Postgraduate medical journal"},{"issue":"10","key":"ref5","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.joca.2013.06.021","article-title":"Osteoarthritis year 2013 in review: clinical","volume":"21","author":"NK Arden","year":"2013","journal-title":"Osteoarthritis and cartilage"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","article-title":"The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis","volume":"6","author":"J Sellam","year":"2010","journal-title":"Nature reviews Rheumatology"},{"issue":"9","key":"ref7","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/art.1780280904","article-title":"Intraarticular variation in synovitis. Local macroscopic and microscopic signs of inflammatory activity are significantly correlated","volume":"28","author":"S Lindblad","year":"1985","journal-title":"Arthritis and rheumatism"},{"issue":"2","key":"ref8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/1759720X12467868","article-title":"Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations","volume":"5","author":"J Sokolove","year":"2013","journal-title":"Therapeutic advances in musculoskeletal disease"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","article-title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)","volume":"21","author":"F. Berenbaum","year":"2013","journal-title":"Osteoarthritis and cartilage"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s00774-007-0761-0","article-title":"Mature and activated osteoclasts exist in the synovium of rapidly destructive coxarthrosis","volume":"25","author":"K Ogawa","year":"2007","journal-title":"Journal of bone and mineral metabolism"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","article-title":"Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review","volume":"20","author":"BJ de Lange-Brokaar","year":"2012","journal-title":"Osteoarthritis and cartilage"},{"issue":"9","key":"ref12","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.joca.2016.04.010","article-title":"Direct in vivo evidence of activated macrophages in human osteoarthritis","volume":"24","author":"VB Kraus","year":"2016","journal-title":"Osteoarthritis and cartilage"},{"issue":"7","key":"ref13","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.joca.2017.01.011","article-title":"Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation","volume":"25","author":"C Manferdini","year":"2017","journal-title":"Osteoarthritis and cartilage"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13075-016-0983-4","article-title":"From osteoarthritic synovium to synovial-derived cells characterization: synovial macrophages are key effector cells","volume":"18","author":"C Manferdini","year":"2016","journal-title":"Arthritis research & therapy"},{"issue":"9","key":"ref15","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.joca.2016.04.013","article-title":"Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis","volume":"24","author":"L Utomo","year":"2016","journal-title":"Osteoarthritis and cartilage"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.joca.2014.05.021","article-title":"Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state","volume":"22","author":"N Fahy","year":"2014","journal-title":"Osteoarthritis and cartilage"},{"issue":"8","key":"ref17","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.joca.2004.03.003","article-title":"Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis","volume":"12","author":"AB Blom","year":"2004","journal-title":"Osteoarthritis and cartilage"},{"key":"ref18","first-page":"1","article-title":"The macrophages in rheumatic diseases","volume":"9","author":"A Laria","year":"2016","journal-title":"Journal of inflammation research"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3389\/fimmu.2014.00532","article-title":"Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages","volume":"5","author":"M Rath","year":"2014","journal-title":"Frontiers in immunology"},{"issue":"5","key":"ref20","first-page":"399","article-title":"Macrophage arginine metabolism to ornithine\/urea or nitric oxide\/citrulline: a life or death issue","volume":"21","author":"CD Mills","year":"2001","journal-title":"Critical reviews in immunology"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/art.27290","article-title":"The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis","volume":"62","author":"J Bondeson","year":"2010","journal-title":"Arthritis and rheumatism"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00018-002-8400-3","article-title":"Molecular pathology and pathobiology of osteoarthritic cartilage","volume":"59","author":"T Aigner","year":"2002","journal-title":"Cellular and molecular life sciences: CMLS"},{"issue":"9","key":"ref23","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1136\/ard.2004.025270","article-title":"Synovial tissue inflammation in early and late osteoarthritis","volume":"64","author":"MJ Benito","year":"2005","journal-title":"Annals of the rheumatic diseases"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.joca.2005.07.012","article-title":"Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes","volume":"13","author":"C Sanchez","year":"2005","journal-title":"Osteoarthritis and cartilage"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fvets.2018.00178","article-title":"The Importance of Subchondral Bone in the Pathophysiology of Osteoarthritis","volume":"5","author":"HL Stewart","year":"2018","journal-title":"Frontiers in veterinary science"},{"issue":"11","key":"ref26","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.joca.2005.03.008","article-title":"Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts","volume":"13","author":"C Sanchez","year":"2005","journal-title":"Osteoarthritis and cartilage"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/ar4405","article-title":"Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes","volume":"15","author":"G Li","year":"2013","journal-title":"Arthritis research & therapy"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1242\/dmm.016881","article-title":"Targets, models and challenges in osteoarthritis research","volume":"8","author":"S Thysen","year":"2015","journal-title":"Disease models & mechanisms"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tvjl.2015.07.011","article-title":"In vitro models for the study of osteoarthritis","volume":"209","author":"CI Johnson","year":"2016","journal-title":"Veterinary journal (London, England: 1997)"},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.joca.2005.10.001","article-title":"Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants","volume":"14","author":"EJ Uitterlinden","year":"2006","journal-title":"Osteoarthritis and cartilage"},{"issue":"4","key":"ref31","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/j.1067-1927.2004.012412.x","article-title":"Pig chondrocyte xenoimplants for human chondral defect repair: an in vitro model","volume":"12","author":"I Fuentes-Boquete","year":"2004","journal-title":"Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society"},{"issue":"Pt 3","key":"ref32","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1042\/bj3290681","article-title":"Intercellular calcium signalling between chondrocytes and synovial cells in co-culture","volume":"329","author":"P D'Andrea","year":"1998","journal-title":"The Biochemical journal"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1042\/bj1840177","article-title":"A cartilage catabolic factor from synovium","volume":"184","author":"JT Dingle","year":"1979","journal-title":"The Biochemical journal"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2460\/ajvr.74.1.40","article-title":"Development of an in vitro model of injury-induced osteoarthritis in cartilage explants from adult horses through application of single-impact compressive overload","volume":"74","author":"CM Lee","year":"2013","journal-title":"American journal of veterinary research"},{"issue":"13\u201314","key":"ref35","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1089\/ten.tea.2013.0444","article-title":"Effect of short-term enzymatic treatment on cell migration and cartilage regeneration: in vitro organ culture of bovine articular cartilage","volume":"20","author":"D Seol","year":"2014","journal-title":"Tissue engineering Part A"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.jbiosc.2016.11.002","article-title":"Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model","volume":"123","author":"M Schmutzer","year":"2017","journal-title":"Journal of bioscience and bioengineering"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1471-2474-14-54","article-title":"Synoviocytes protect cartilage from the effects of injury in vitro","volume":"14","author":"CM Lee","year":"2013","journal-title":"BMC musculoskeletal disorders"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/jor.20111","article-title":"Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage","volume":"24","author":"CA Huser","year":"2006","journal-title":"Journal of orthopaedic research: official publication of the Orthopaedic Research Society"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"R223","DOI":"10.1186\/ar4424","article-title":"Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1beta","volume":"15","author":"A Williams","year":"2013","journal-title":"Arthritis research & therapy"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/ten.teb.2011.0077","article-title":"Hydrogels for the repair of articular cartilage defects","volume":"17","author":"KL Spiller","year":"2011","journal-title":"Tissue engineering Part B, Reviews"},{"key":"ref41","article-title":"Mikroskopische Technik","author":"B. Romeis","year":"1989"},{"issue":"10","key":"ref42","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.joca.2007.03.017","article-title":"Measurement of synovial fluid volume using urea","volume":"15","author":"VB Kraus","year":"2007","journal-title":"Osteoarthritis and cartilage"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"9696","DOI":"10.1007\/s11357-014-9696-2","article-title":"Peritoneal exudate cells from long-lived rats exhibit increased IL-10\/IL-1beta expression ratio and preserved NO\/urea ratio following LPS-stimulation in vitro","volume":"36","author":"M Dimitrijevic","year":"2014","journal-title":"Age (Dordrecht, Netherlands)"},{"key":"ref44","doi-asserted-by":"crossref","DOI":"10.1002\/0471142735.im1422s93","article-title":"Quantitative assessment of macrophage functions in repair and fibrosis","author":"TA Wynn","year":"2011","journal-title":"Current protocols in immunology"},{"issue":"1","key":"ref45","first-page":"33","article-title":"Least-Squares Means: The R Package lsmeans","volume":"69","author":"RV Lenth","year":"2016","journal-title":"Least-Squares Means: The R Package lsmeans"},{"issue":"10","key":"ref46","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1002\/art.10531","article-title":"Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro","volume":"46","author":"B Bau","year":"2002","journal-title":"Arthritis and rheumatism"},{"issue":"1","key":"ref47","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/art.11433","article-title":"Expression profiling of metalloproteinases and their inhibitors in cartilage","volume":"50","author":"L Kevorkian","year":"2004","journal-title":"Arthritis and rheumatism"},{"issue":"1\u20132","key":"ref48","first-page":"118","article-title":"Co-culture of mechanically injured cartilage with joint capsule tissue alters chondrocyte expression patterns and increases ADAMTS5 production","volume":"489","author":"JH Lee","year":"2009","journal-title":"Archives of biochemistry and biophysics"},{"issue":"4","key":"ref49","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1600-0838.2009.00911.x","article-title":"Potent inhibition of cartilage biosynthesis by coincubation with joint capsule through an IL-1-independent pathway","volume":"19","author":"P Patwari","year":"2009","journal-title":"Scandinavian journal of medicine & science in sports"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0214709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T12:30:41Z","timestamp":1589027441000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0214709"}},"subtitle":[],"editor":[{"given":"Rasheed","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,4,2]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0214709","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,2]]}}}