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dc.contributor.authorVarela Eirín, Marta
dc.contributor.authorCarpintero Fernández, Paula
dc.contributor.authorGuitián Caamaño, Amanda
dc.contributor.authorVarela Vázquez, Adrian
dc.contributor.authorGarcía Yuste, Alejandro
dc.contributor.authorSánchez Temprano, Agustín
dc.contributor.authorBravo López, Susana Belén
dc.contributor.authorYáñez Cabanas, José
dc.contributor.authorFonseca Capdevila, Eduardo 
dc.contributor.authorLargo, Raquel
dc.contributor.authorMobasheri, Ali
dc.contributor.authorCaeiro Rey, José Ramón 
dc.contributor.authorMayán Santos, María Dolores
dc.date.accessioned2022-11-24T12:08:39Z
dc.date.available2022-11-24T12:08:39Z
dc.date.issued2022-08-05
dc.identifier.otherhttps://pubmed.ncbi.nlm.nih.gov/35931686/es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/17063
dc.description.abstractThe accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related diseases such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin 43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling programme and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighbouring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for future studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.es
dc.description.sponsorshipHealth Institute ‘Carlos III’ (ISCIII, Spain), the European Regional Development Fund, ‘A way of making Europe’ from the European Union (to MDM): grant PI19/00145es
dc.description.sponsorshipJoint Transnational Call for Proposals for “European Innovative Research & Technological Development Projects in Nanomedicine” EURONANOMED III (AC21_2/00026) (to MDM)es
dc.description.sponsorshipXunta de Galicia (IN607B2020/12) (to MDM)es
dc.description.sponsorshipH2020, Future and Emerging Technologies (grant 858014 “PANACHE”) to MDMes
dc.language.isoenges
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAging*
dc.subject.meshConnexin 43*
dc.subject.meshChondrocytes*
dc.subject.meshPhenotype*
dc.subject.meshOsteoarthritis*
dc.titleExtracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progressiones
dc.typeArtigoes
dc.rights.licenseAttribution 4.0 International*
dc.rights.holderAutoreses
dc.identifier.doi10.1038/s41419-022-05089-w
dc.identifier.pmid35931686
dc.issue.number8es
dc.journal.titleCell Death and Diseasees
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Biomédica da Coruña (INIBIC)es
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)es
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostelaes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Traumatoloxíaes
dc.page.initial681es
dc.relation.projectIDISCIII/PI19/00145es
dc.relation.projectIDEURONANOMED III7AC21_2/00026es
dc.relation.projectIDXunta de Galicia/IN607B2020/12es
dc.relation.projectIDH2020, Future and Emerging Technologies/858014 “PANACHE”es
dc.relation.publisherversionhttps://www.nature.com/articles/s41419-022-05089-wes
dc.rights.accessRightsopenAccesses
dc.subject.decsfenotipo*
dc.subject.decsconexina 43*
dc.subject.decsenvejecimiento*
dc.subject.decscondrocitos*
dc.subject.decsosteoartritis*
dc.subject.keywordINIBICes
dc.subject.keywordCHUSes
dc.subject.keywordIDISes
dc.typefidesArtigo Científico (inclue Orixinal, Orixinal breve, Revisión Sistemática e Meta-análisis)es
dc.typesophosArtículo Originales
dc.volume.number13es


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