Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis.
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Authors
Southam, Lorraine
Fontalis, Andreas
Clark, Matthew J
Jayasuriya, Raveen L
Swift, Diane
Shah, Karan M
Brooks, Roger
Publication Date
2021-08Journal Title
Ann Rheum Dis
ISSN
0003-4967
Publisher
BMJ
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Steinberg, J., Southam, L., Fontalis, A., Clark, M. J., Jayasuriya, R. L., Swift, D., Shah, K. M., et al. (2021). Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis.. Ann Rheum Dis https://doi.org/10.1136/annrheumdis-2020-219760
Abstract
OBJECTIVES: To determine how gene expression profiles in osteoarthritis joint tissues relate to patient phenotypes and whether molecular subtypes can be reproducibly captured by a molecular classification algorithm. METHODS: We analysed RNA sequencing data from cartilage and synovium in 113 osteoarthritis patients, applying unsupervised clustering and Multi-Omics Factor Analysis to characterise transcriptional profiles. We tested the association of the molecularly defined patient subgroups with clinical characteristics from electronic health records. RESULTS: We detected two patient subgroups in low-grade cartilage (showing no/minimal degeneration, cartilage normal/softening only), with differences associated with inflammation, extracellular matrix-related and cell adhesion pathways. The high-inflammation subgroup was associated with female sex (OR 4.12, p=0.0024) and prescription of proton pump inhibitors (OR 4.21, p=0.0040). We identified two independent patient subgroupings in osteoarthritis synovium: one related to inflammation and the other to extracellular matrix and cell adhesion processes. A seven-gene classifier including MMP13, APOD, MMP2, MMP1, CYTL1, IL6 and C15orf48 recapitulated the main axis of molecular heterogeneity in low-grade knee osteoarthritis cartilage (correlation ρ=-0.88, p<10-10) and was reproducible in an independent patient cohort (ρ=-0.85, p<10-10). CONCLUSIONS: These data support the reproducible stratification of osteoarthritis patients by molecular subtype and the exploration of new avenues for tailored treatments.
Sponsorship
ARTHRITIS RESEARCH UK (21156)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/R015635/1)
Identifiers
External DOI: https://doi.org/10.1136/annrheumdis-2020-219760
This record's URL: https://www.repository.cam.ac.uk/handle/1810/321872
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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