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Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model
dc.contributor.author | Araújo, Nuna | |
dc.contributor.author | Viegas, Carla S B | |
dc.contributor.author | Zubía, Eva | |
dc.contributor.author | Magalhaes Silva, Joana Cristina | |
dc.contributor.author | Ramos, Acácio | |
dc.contributor.author | Carvalho, Maria M | |
dc.contributor.author | Cruz, Henrique | |
dc.contributor.author | Sousa, João Paulo | |
dc.contributor.author | BLANCO GARCIA, FRANCISCO JAVIER | |
dc.contributor.author | Vermeer, Cees | |
dc.contributor.author | Simes, Dina C | |
dc.date.accessioned | 2022-03-08T08:51:32Z | |
dc.date.available | 2022-03-08T08:51:32Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1660-3397 | |
dc.identifier.other | https://www.ncbi.nlm.nih.gov/pubmed/33297528 | es |
dc.identifier.uri | http://hdl.handle.net/20.500.11940/16223 | |
dc.description.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-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.rights | Atribución 4.0 Internacional | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.mesh | Gene Expression | * |
dc.subject.mesh | Anti-Inflammatory Agents | * |
dc.subject.mesh | Chondrocytes | * |
dc.subject.mesh | Diterpenes | * |
dc.subject.mesh | Coculture Techniques | * |
dc.subject.mesh | Osteoarthritis | * |
dc.subject.mesh | Cyanobacteria | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | Antirheumatic Agents | * |
dc.subject.mesh | Durapatite | * |
dc.subject.mesh | Primary Cell Culture | * |
dc.subject.mesh | Interleukin-1beta | * |
dc.subject.mesh | Inflammation | * |
dc.subject.mesh | Cartilage | * |
dc.title | Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model | en |
dc.type | Journal Article | es |
dc.authorsophos | Araújo, 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.doi | 10.3390/md18120624 | |
dc.identifier.pmid | 33297528 | |
dc.identifier.sophos | 35936 | |
dc.issue.number | 12 | es |
dc.journal.title | Marine Drugs | es |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de A Coruña - Complexo Hospitalario Universitario de A Coruña::Reumatoloxía | es |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Biomédica da Coruña (INIBIC) | es |
dc.relation.publisherversion | https://mdpi-res.com/d://attachment/marinedrugs/marinedrugs-18-00624/article://deploy/marinedrugs-18-00624-v2.pdf | es |
dc.rights.accessRights | openAccess | |
dc.subject.decs | Cyanobacteria | * |
dc.subject.decs | expresión génica | * |
dc.subject.decs | inflamación | * |
dc.subject.decs | antirreumáticos | * |
dc.subject.decs | condrocitos | * |
dc.subject.decs | técnicas de cocultivo | * |
dc.subject.decs | diterpenos | * |
dc.subject.decs | cartílago | * |
dc.subject.decs | cultivo celular primario | * |
dc.subject.decs | durapatita | * |
dc.subject.decs | humanos | * |
dc.subject.decs | interleucina-1beta | * |
dc.subject.decs | antiinflamatorios | * |
dc.subject.decs | osteoartritis | * |
dc.subject.keyword | CHUAC | es |
dc.subject.keyword | INIBIC | es |
dc.typefides | Artículo Original | es |
dc.typesophos | Artículo Original | es |
dc.volume.number | 18 | es |