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Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.
Rheumatology 57, 1481-1489 (2018)
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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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2018
HGF-reported in Year
2018
ISSN (print) / ISBN
1462-0324
e-ISSN
1462-0332
Journal
Rheumatology
Quellenangaben
Volume: 57,
Issue: 8,
Pages: 1481-1489
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-506700-001
PubMed ID
29741735
Erfassungsdatum
2020-01-29