Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis.
Clark, Matthew J
Jayasuriya, Raveen L
Shah, Karan M
Ann Rheum Dis
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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
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.
ARTHRITIS RESEARCH UK (21156)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/R015635/1)
External DOI: https://doi.org/10.1136/annrheumdis-2020-219760
This record's URL: https://www.repository.cam.ac.uk/handle/1810/321872
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/