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dc.contributor.authorAraújo, Nuna
dc.contributor.authorViegas, Carla S B
dc.contributor.authorZubía, Eva
dc.contributor.authorMagalhaes Silva, Joana Cristina
dc.contributor.authorRamos, Acácio
dc.contributor.authorCarvalho, Maria M
dc.contributor.authorCruz, Henrique
dc.contributor.authorSousa, João Paulo
dc.contributor.authorBLANCO GARCIA, FRANCISCO JAVIER 
dc.contributor.authorVermeer, Cees
dc.contributor.authorSimes, Dina C
dc.date.accessioned2022-03-08T08:51:32Z
dc.date.available2022-03-08T08:51:32Z
dc.date.issued2020
dc.identifier.issn1660-3397
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/33297528es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/16223
dc.description.abstractOsteoarthritis (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-1beta (IL-1beta) 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-kappaB gene expression and decreased phosphorylated IkBalpha/total IkBalpha 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-kappaB signaling pathways, with high therapeutic potential.en
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshGene Expression*
dc.subject.meshAnti-Inflammatory Agents*
dc.subject.meshChondrocytes*
dc.subject.meshDiterpenes*
dc.subject.meshCoculture Techniques*
dc.subject.meshOsteoarthritis*
dc.subject.meshCyanobacteria*
dc.subject.meshHumans*
dc.subject.meshAntirheumatic Agents*
dc.subject.meshDurapatite*
dc.subject.meshPrimary Cell Culture*
dc.subject.meshInterleukin-1beta*
dc.subject.meshInflammation*
dc.subject.meshCartilage*
dc.titleAmentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Modelen
dc.typeJournal Articlees
dc.authorsophosAraújo, Nuna;Viegas, Carla S B;Zubía, Eva;Magalhães, Joana;Ramos, Acácio;Carvalho, Maria M;Cruz, Henrique;Sousa, João Paulo;Blanco, Francisco J;Vermeer, Cees;Simes, Dina C
dc.identifier.doi10.3390/md18120624
dc.identifier.pmid33297528
dc.identifier.sophos35936
dc.issue.number12es
dc.journal.titleMarine Drugses
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de A Coruña - Complexo Hospitalario Universitario de A Coruña::Reumatoloxíaes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Biomédica da Coruña (INIBIC)es
dc.relation.publisherversionhttps://mdpi-res.com/d://attachment/marinedrugs/marinedrugs-18-00624/article://deploy/marinedrugs-18-00624-v2.pdfes
dc.rights.accessRightsopenAccess
dc.subject.decsCyanobacteria *
dc.subject.decsexpresión génica *
dc.subject.decsinflamación *
dc.subject.decsantirreumáticos *
dc.subject.decscondrocitos *
dc.subject.decstécnicas de cocultivo *
dc.subject.decsditerpenos *
dc.subject.decscartílago *
dc.subject.decscultivo celular primario *
dc.subject.decsdurapatita *
dc.subject.decshumanos *
dc.subject.decsinterleucina-1beta *
dc.subject.decsantiinflamatorios *
dc.subject.decsosteoartritis *
dc.subject.keywordCHUACes
dc.subject.keywordINIBICes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number18es


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Atribución 4.0 Internacional
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