{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:10:50Z","timestamp":1789708250044,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Operational Programme Integrated Infrastructure, funded by the ERDF","award":["ITMS2014+:313011V455"],"award-info":[{"award-number":["ITMS2014+:313011V455"]}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["APVV17-0118"],"award-info":[{"award-number":["APVV17-0118"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Grant Agency of the Ministry of Education, Science, Research and Sports of the Slovak Republic","award":["VEGA no.1\/0598\/20"],"award-info":[{"award-number":["VEGA no.1\/0598\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is a lack of in vitro models able to plausibly represent the inflammation microenvironment of knee osteoarthritis (OA). We analyzed the molecules released from OA tissues (synovial membrane, cartilage, infrapatellar fat pad) and investigated whether the stimulation of human synovial fibroblasts (SFs), with synthetic cytokines (IL-1\u03b2 and TNF-\u03b1 or IFN-\u03b3) or conditioned media (CM) from OA tissues, influence the SFs\u2019 response, in the sense of pro-inflammatory cytokines, chemokines, growth factors, and degradative enzymes modulation. Human SFs were obtained from OA synovial membranes. SFs and their CM were analyzed for biomarkers, proliferation rate, protein profile and gene expression, before and after stimulation. Real-time PCR and multiplex assays quantified OA-related gene expression and biomolecule production. Unlike other activators, CM from OA synovial membrane (CM-SM), significantly up-regulated all genes of interest (IL-6, IL-8, MMP-1, MMP-3, RANTES, MCP-1, TSG-6, YKL-40) in SFs. Multiplex immunoassay analysis showed that levels of OA-related cytokines (IL-6, IL-8, MCP 1, IL-1Ra), chemokine (RANTES) and growth factor (VEGF), produced by CM-SM stimulated SFs, increased significantly compared to non-stimulated SFs. Molecules released from the SM from OA patients induces OA-like changes in vitro, in specific OA synovial populations (SFs). These findings promote the use and establish a compelling in vitro model that simulates the versatility and complexity of the OA disease. This model, in the future, will allow us to study new cell therapies or test drugs by reducing or avoiding animal models.<\/jats:p>","DOI":"10.3390\/ijms23052475","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T07:22:35Z","timestamp":1645687355000},"page":"2475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Role of Synovial Membrane in the Development of a Potential In Vitro Model of Osteoarthritis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3038-7520","authenticated-orcid":false,"given":"Denisa","family":"Harvanova","sequence":"first","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9086-3621","authenticated-orcid":false,"given":"Jana","family":"Matejova","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-0655","authenticated-orcid":false,"given":"Lucia","family":"Slovinska","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4276-3722","authenticated-orcid":false,"given":"Marek","family":"Lacko","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology of Locomotors Apparatus, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slavomira","family":"Gulova","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia Kolesar","family":"Fecskeova","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-1860","authenticated-orcid":false,"given":"Jana","family":"Janockova","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timea","family":"Spakova","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rosocha","sequence":"additional","affiliation":[{"name":"Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Trieda SNP 1, 04011 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: Toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1749-6632.2009.05240.x","article-title":"Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis","volume":"1192","author":"Goldring","year":"2010","journal-title":"Ann. 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