Show simple item record

dc.contributor.authorSteinberg, Jen_US
dc.contributor.authorBrooks, RAen_US
dc.contributor.authorSoutham, Len_US
dc.contributor.authorBhatnagar, Sen_US
dc.contributor.authorRoumeliotis, TIen_US
dc.contributor.authorHatzikotoulas, Ken_US
dc.contributor.authorZengini, Een_US
dc.contributor.authorWilkinson, JMen_US
dc.contributor.authorChoudhary, JSen_US
dc.contributor.authorMcCaskie, AWen_US
dc.contributor.authorZeggini, Een_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-25T16:08:04Z
dc.date.issued2018-08-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29741735en_US
dc.identifier4993770en_US
dc.identifier.citationRheumatology (Oxford), 2018, 57 (8), pp. 1481 - 1489en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3084
dc.identifier.eissn1462-0332en_US
dc.identifier.doi10.1093/rheumatology/key101en_US
dc.description.abstractObjectives: To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. Methods: We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Results: Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. Conclusion: We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression.en_US
dc.format.extent1481 - 1489en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectCartilage, Articularen_US
dc.subjectChondrocytesen_US
dc.subjectChromatography, Liquiden_US
dc.subjectDNA Methylationen_US
dc.subjectEpigenomicsen_US
dc.subjectFemaleen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectMass Spectrometryen_US
dc.subjectMiddle Ageden_US
dc.subjectOsteoarthritis, Hipen_US
dc.subjectProteomicsen_US
dc.subjectRNAen_US
dc.titleWidespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/rheumatology/key101en_US
rioxxterms.licenseref.startdate2018-08-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfRheumatology (Oxford)en_US
pubs.issue8en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.publication-statusPublisheden_US
pubs.volume57en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorChoudhary, Jyotien_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/