Effects of 5-aza-2´-deoxycytidine on primary human chondrocytes from osteoarthritic patients

dc.contributor.authorKadler, Shirin
dc.contributor.authorVural, Özlem
dc.contributor.authorRosowski, Jennifer
dc.contributor.authorReiners-Schramm, Luzia
dc.contributor.authorLauster, Roland
dc.contributor.authorRosowski, Mark
dc.date.accessioned2020-09-30T20:31:59Z
dc.date.available2020-09-30T20:31:59Z
dc.date.issued2020-06-23
dc.description.abstractChondrocytes, comparable to many cells from the connective tissue, dedifferentiate and end up in a similar fibroblastoid cell type, marked by the loss of the specific expression pattern. Here, chondrocytes isolated from osteoarthritic (OA) patients were investigated. The OA chondrocytes used in this work were not affected by the loss of specific gene expression upon cell culture. The mRNA levels of known cartilage markers, such as SOX5, SOX6, SOX9, aggrecan and proteoglycan 4, remained unchanged. Since chondrocytes from OA and healthy tissue show different DNA methylation patterns, the underlying mechanisms of cartilage marker maintenance were investigated with a focus on the epigenetic modification by DNA methylation. The treatment of dedifferentiated chondrocytes with the DNA methyltransferase inhibitor 5-aza-2´-deoxycytidine (5-aza-dC) displayed no considerable impact on the maintenance of marker gene expression observed in the dedifferentiated state, while the chondrogenic differentiation capacity was compromised. On the other hand, the pre-cultivation with 5-aza-dC improved the osteogenesis and adipogenesis of OA chondrocytes. Contradictory to these effects, the DNA methylation levels were not reduced after treatment for four weeks with 1 μM 5-aza-dC. In conclusion, 5-aza-dC affects the differentiation capacity of OA chondrocytes, while the global DNA methylation level remains stable. Furthermore, dedifferentiated chondrocytes isolated from late-stage OA patients represent a reliable cell source for in vitro studies and disease models without the need for additional alterations.en
dc.description.sponsorshipDFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berlinen
dc.identifier.eissn1932-6203
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/11731
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-10620
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc500 Naturwissenschaften und Mathematikde
dc.subject.ddc610 Medizin und Gesundheitde
dc.subject.otherchondrocytesen
dc.subject.otherDNA methylationen
dc.subject.othercartilageen
dc.subject.otherosteoarthritisen
dc.subject.othercell differentiationen
dc.subject.othergene expressionen
dc.subject.othersafranin stainingen
dc.subject.othercollagensen
dc.titleEffects of 5-aza-2´-deoxycytidine on primary human chondrocytes from osteoarthritic patientsen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumbere0234641en
dcterms.bibliographicCitation.doi10.1371/journal.pone.0234641en
dcterms.bibliographicCitation.issue6en
dcterms.bibliographicCitation.journaltitlePLOS ONEen
dcterms.bibliographicCitation.originalpublishernamePLOSen
dcterms.bibliographicCitation.originalpublisherplaceSan Francisco, California, USen
dcterms.bibliographicCitation.volume15en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Medizinische Biotechnologiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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