Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.
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Date
2018-08-01Author
Steinberg, J
Brooks, RA
Southam, L
Bhatnagar, S
Roumeliotis, TI
Hatzikotoulas, K
Zengini, E
Wilkinson, JM
Choudhary, JS
McCaskie, AW
Zeggini, E
Type
Journal Article
Metadata
Show full item recordAbstract
OBJECTIVES: 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.
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Subject
Cartilage, Articular
Chondrocytes
Humans
Osteoarthritis, Hip
RNA
Chromatography, Liquid
Proteomics
DNA Methylation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Mass Spectrometry
Genome-Wide Association Study
Epigenomics
Language
eng
Date accepted
2018-05-08
License start date
2018-08
Citation
Rheumatology (Oxford, England), 2018, 57 (8), pp. 1481 - 1489
Publisher
OXFORD UNIV PRESS