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Amentadione from the alga Cystoseira usneoides as a novel osteoarthritis trotective agent in an ex vivo co-culture OA Model

2020Journal article Open access
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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.accessioned2021-01-14T17:45:35Z
dc.date.available2021-01-14T17:45:35Z
dc.date.issued2020
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-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.sponsorshipFCT: DL57/2016/CP1361/CT0006/ UIDB/04326/2020/ SFRH/BD/111824/2015pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/md18120624pt_PT
dc.identifier.eissn1660-3397
dc.identifier.urihttp://hdl.handle.net/10400.1/14964
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectChondrocytespt_PT
dc.subjectCartilage explantspt_PT
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.subjectSynoviocytespt_PT
dc.titleAmentadione from the alga Cystoseira usneoides as a novel osteoarthritis trotective agent in an ex vivo co-culture OA Modelpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue12pt_PT
oaire.citation.startPage624pt_PT
oaire.citation.titleMarine Drugspt_PT
oaire.citation.volume18pt_PT
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
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3423e71b-934d-4da7-9c81-4e56c7930252
relation.isAuthorOfPublication33984b3c-ffac-477a-896a-ddbf7aced4e3
relation.isAuthorOfPublication31bac96d-1d01-4b8f-8f2b-9da4be31ea41
relation.isAuthorOfPublication.latestForDiscovery33984b3c-ffac-477a-896a-ddbf7aced4e3

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