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Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis.

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dc.contributor.authorEldridge, Suzanne E
dc.contributor.authorBarawi, Aida
dc.contributor.authorWang, Hui
dc.contributor.authorRoelofs, Anke J
dc.contributor.authorKaneva, Magdalena
dc.contributor.authorGuan, Zeyu
dc.contributor.authorLydon, Helen
dc.contributor.authorThomas, Bethan L
dc.contributor.authorThorup, Anne-Sophie
dc.contributor.authorFernandez, Beatriz F
dc.contributor.authorCaxaria, Sara
dc.contributor.authorStrachan, Danielle
dc.contributor.authorAli, Ahmed
dc.contributor.authorShanmuganathan, Kanatheepan
dc.contributor.authorPitzalis, Costantino
dc.contributor.authorWhiteford, James R
dc.contributor.authorHenson, Frances
dc.contributor.authorMcCaskie, Andrew W
dc.contributor.authorDe Bari, Cosimo
dc.contributor.authorDell'Accio, Francesco
dc.contributor.orcidEldridge, Suzanne E [0000-0002-1630-6261]
dc.contributor.orcidBarawi, Aida [0000-0001-5504-9184]
dc.contributor.orcidKaneva, Magdalena [0000-0003-3822-749X]
dc.contributor.orcidGuan, Zeyu [0000-0003-3050-4210]
dc.contributor.orcidLydon, Helen [0000-0003-4012-7631]
dc.contributor.orcidThorup, Anne-Sophie [0000-0002-0435-4071]
dc.contributor.orcidFernandez, Beatriz F [0000-0002-8612-0251]
dc.contributor.orcidCaxaria, Sara [0000-0002-8434-8332]
dc.contributor.orcidStrachan, Danielle [0000-0002-9544-6341]
dc.contributor.orcidAli, Ahmed [0000-0002-2750-399X]
dc.contributor.orcidShanmuganathan, Kanatheepan [0000-0003-2731-9508]
dc.contributor.orcidPitzalis, Costantino [0000-0003-1326-5051]
dc.contributor.orcidWhiteford, James R [0000-0002-8967-7389]
dc.contributor.orcidHenson, Frances [0000-0002-3518-1492]
dc.contributor.orcidMcCaskie, Andrew W [0000-0001-6476-0832]
dc.contributor.orcidDell'Accio, Francesco [0000-0003-4137-3770]
dc.date.accessioned2020-10-23T23:30:49Z
dc.date.available2020-10-23T23:30:49Z
dc.date.issued2020-09-02
dc.description.abstractCartilage loss leads to osteoarthritis, the most common cause of disability for which there is no cure. Cartilage regeneration, therefore, is a priority in medicine. We report that agrin is a potent chondrogenic factor and that a single intraarticular administration of agrin induced long-lasting regeneration of critical-size osteochondral defects in mice, with restoration of tissue architecture and bone-cartilage interface. Agrin attracted joint resident progenitor cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signaling downstream of β-catenin, induced expression of the chondrogenic stem cell marker GDF5 and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, an agrin-containing collagen gel resulted in long-lasting regeneration of bone and cartilage, which promoted increased ambulatory activity. Our findings support the therapeutic use of agrin for joint surface regeneration.
dc.format.mediumPrint
dc.identifier.doi10.17863/CAM.58988
dc.identifier.eissn1946-6242
dc.identifier.issn1946-6234
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311896
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.publisher.urlhttp://dx.doi.org/10.1126/scitranslmed.aax9086
dc.rightsAll rights reserved
dc.subjectAgrin
dc.subjectAnimals
dc.subjectCartilage, Articular
dc.subjectCell Differentiation
dc.subjectChondrocytes
dc.subjectChondrogenesis
dc.subjectMice
dc.subjectSheep
dc.subjectTissue Scaffolds
dc.titleAgrin induces long-term osteochondral regeneration by supporting repair morphogenesis.
dc.typeArticle
dcterms.dateAccepted2020-08-13
prism.issueIdentifier559
prism.publicationDate2020
prism.publicationNameSci Transl Med
prism.volume12
pubs.funder-project-idMedical Research Council (MR/L022893/1)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idMedical Research Council (MR/R015635/1)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
rioxxterms.licenseref.startdate2020-09
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1126/scitranslmed.aax9086

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