{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:26:38Z","timestamp":1770776798535,"version":"3.50.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["transitional provision DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["transitional provision DL57\/2016\/CP1361\/CT0006"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["project UIDB\/04326\/2020"],"award-info":[{"award-number":["project UIDB\/04326\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["fellowship SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["fellowship SFRH\/BD\/111824\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1\u03b2 (IL-1\u03b2) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-\u03baB gene expression and decreased phosphorylated IkB\u03b1\/total IkB\u03b1 ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-\u03baB signaling pathways, with high therapeutic potential.<\/jats:p>","DOI":"10.3390\/md18120624","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T21:37:42Z","timestamp":1607377062000},"page":"624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Nuna","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal"}]},{"given":"Carla S. B.","family":"Viegas","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal"},{"name":"GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal"}]},{"given":"Eva","family":"Zub\u00eda","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Marine and Environmental Sciences, University of Cadiz, 11510 Puerto Real (C\u00e1diz), Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-2209","authenticated-orcid":false,"given":"Joana","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Unidad de Medicina Regenerativa, Grupo de Investigaci\u00f3n en Reumatolog\u00eda (GIR), Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complejo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Sergas, 15006 A Coru\u00f1a, Spain"},{"name":"Agrupaci\u00f3n Estrat\u00e9gica CICA-INIBIC, Universidade da Coru\u00f1a (UDC), 15006 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER), 28029 Madrid, Spain"}]},{"given":"Ac\u00e1cio","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Hospital Particular do Algarve (HPA), 8005-226 Gambelas-Faro, Portugal"}]},{"given":"Maria M.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Hospital Particular do Algarve (HPA), 8005-226 Gambelas-Faro, Portugal"}]},{"given":"Henrique","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Hospital Particular do Algarve (HPA), 8005-226 Gambelas-Faro, Portugal"}]},{"given":"Jo\u00e3o Paulo","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Hospital Particular do Algarve (HPA), 8005-226 Gambelas-Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-7635","authenticated-orcid":false,"given":"Francisco J.","family":"Blanco","sequence":"additional","affiliation":[{"name":"Unidad de Medicina Regenerativa, Grupo de Investigaci\u00f3n en Reumatolog\u00eda (GIR), Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complejo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Sergas, 15006 A Coru\u00f1a, Spain"},{"name":"Agrupaci\u00f3n Estrat\u00e9gica CICA-INIBIC, Universidade da Coru\u00f1a (UDC), 15006 A Coru\u00f1a, Spain"}]},{"given":"Cees","family":"Vermeer","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute CARIM, Maastricht University, 6229 EV Maastricht, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5145-4753","authenticated-orcid":false,"given":"Dina C.","family":"Simes","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal"},{"name":"GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/art.23176","article-title":"Estimates of the prevalence of arthritis and other rheumatic conditions in the United States","volume":"58","author":"Lawrence","year":"2008","journal-title":"Part II Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Moe, R.H., Uhlig, T., Kjeken, I., Hagen, K.B., Kvien, T.K., and Grotle, M. 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