Araújo, NunaViegas, Carla S.B.Zubía, EvaMagalhães, JoanaRamos, AcácioCarvalho, Maria M.Cruz, HenriqueSousa, Joao PauloBlanco García, Francisco JVermeer, CeesSimes, DC2021-01-132021-01-132020-12-07Araújo N, Viegas CSB, Zubía E, Magalhães J, Ramos A, Carvalho MM, Cruz H, Sousa JP, Blanco FJ, Vermeer C, Simes DC. Amentadione from the alga cystoseira usneoides as a novel osteoarthritis protective agent in an ex vivo co-culture OA model. Mar Drugs. 2020 Dec 7;18(12):624.1660-3397http://hdl.handle.net/2183/27098[Abstract] 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-1β (IL-1β) 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-κB gene expression and decreased phosphorylated IkBα/total IkBα 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-κB signaling pathways, with high therapeutic potential.engCreative Commons Attribution 4.0 International License (CC-BY 4.0)http://creativecommons.org/licenses/by/4.0/OsteoarthritisAmentadionePreclinical osteoarthritis modelsMarine compoundsCystoseira usneoidesInflammationMineralizationChondrocytesSynoviocytesCartilage explantsjournal articleopen access