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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.authorAraujo, Nuna C. P.
dc.contributor.authorViegas, Carla
dc.contributor.authorZubía, Eva
dc.contributor.authorMagalhães, Joana
dc.contributor.authorRamos, Acácio
dc.contributor.authorCarvalho, Maria M.
dc.contributor.authorCruz, Henrique
dc.contributor.authorSousa, João Paulo
dc.contributor.authorBlanco, Francisco J.
dc.contributor.authorVermeer, Cees
dc.contributor.authorSimes, Dina
dc.date.accessioned2021-01-14T11:52:31Z
dc.date.available2021-01-14T11:52:31Z
dc.date.issued2020-12-07
dc.date.updated2021-01-08T14:44:21Z
dc.description.abstractOsteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga <i>Cystoseira usneoides</i>, 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.pt_PT
dc.description.sponsorshipThis research was funded by the Portuguese national funds from FCT—Foundation for Science and Technology through the transitional provision DL57/2016/CP1361/CT0006 and project UIDB/04326/2020. N Araújo is the recipient of the Portuguese Science and Technology Foundation (FCT) fellowship SFRH/BD/111824/2015.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifierdoi: 10.3390/md18120624
dc.identifier.citationMarine Drugs 18 (12): 624 (2020)pt_PT
dc.identifier.doi10.3390/md18120624pt_PT
dc.identifier.issn1660-3397
dc.identifier.urihttp://hdl.handle.net/10400.1/14960
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationAlgarve Centre for Marine Sciences
dc.relationInterplay between mineralization and inflammation in vascular calcification and osteoarthritis: extracellular vesicles and marine bioactive compounds as a therapeutic approach
dc.subjectOsteoarthritispt_PT
dc.subjectAmentadionept_PT
dc.subjectPreclinical osteoarthritis modelspt_PT
dc.subjectMarine compoundspt_PT
dc.subjectCystoseira usneoidespt_PT
dc.subjectInflammationpt_PT
dc.subjectMineralizationpt_PT
dc.subjectChondrocytespt_PT
dc.subjectSynoviocytespt_PT
dc.subjectCartilage explantspt_PT
dc.titleAmentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Modelpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleInterplay between mineralization and inflammation in vascular calcification and osteoarthritis: extracellular vesicles and marine bioactive compounds as a therapeutic approach
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F111824%2F2015/PT
oaire.citation.issue12pt_PT
oaire.citation.startPage624pt_PT
oaire.citation.titleMarine Drugspt_PT
oaire.citation.volume18pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameAraujo
person.familyNameViegas
person.familyNameSimes
person.givenNameNuna
person.givenNameCarla
person.givenNameDina
person.identifier.ciencia-idC414-F596-EEC6
person.identifier.orcid0000-0002-7602-0150
person.identifier.orcid0000-0002-5765-3665
person.identifier.orcid0000-0002-5145-4753
person.identifier.ridN-8531-2013
person.identifier.ridN-6695-2014
person.identifier.ridN-2789-2014
person.identifier.scopus-author-id8656310300
person.identifier.scopus-author-id7201884723
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication33984b3c-ffac-477a-896a-ddbf7aced4e3
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relation.isAuthorOfPublication.latestForDiscovery33984b3c-ffac-477a-896a-ddbf7aced4e3
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