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Steinberg J, Southam L, Fontalis A, et al. Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis. Ann Rheum Dis. 2021;doi: 10.1136/annrheumdis-2020-219760.
Steinberg, J., Southam, L., Fontalis, A., Clark, M. J., Jayasuriya, R. L., Swift, D., Shah, K. M., Brooks, R. A., McCaskie, A. W., Wilkinson, J. M., & Zeggini, E. (2021). Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis. Annals of the rheumatic diseases, . https://doi.org/10.1136/annrheumdis-2020-219760
Steinberg, Julia, et al. "Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis." Annals of the rheumatic diseases vol. (2021). doi: https://doi.org/10.1136/annrheumdis-2020-219760
Steinberg J, Southam L, Fontalis A, Clark MJ, Jayasuriya RL, Swift D, Shah KM, Brooks RA, McCaskie AW, Wilkinson JM, Zeggini E. Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis. Ann Rheum Dis. 2021 Apr 26; doi: 10.1136/annrheumdis-2020-219760. Epub 2021 Apr 26. PMID: 33903094; PMCID: PMC8292595.
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Ann Rheum Dis. 2021 Apr 26; doi: 10.1136/annrheumdis-2020-219760. Epub 2021 Apr 26.

Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis.

Annals of the rheumatic diseases

Julia Steinberg, Lorraine Southam, Andreas Fontalis, Matthew J Clark, Raveen L Jayasuriya, Diane Swift, Karan M Shah, Roger A Brooks, Andrew W McCaskie, Jeremy Mark Wilkinson, Eleftheria Zeggini

Affiliations

  1. Institute for Translational Genomics, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.
  2. Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia.
  3. Wellcome Sanger Institute, Hinxton, UK.
  4. Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK.
  5. Division of Trauma & Orthopaedic Surgery, University of Cambridge, Cambridge, UK.
  6. Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK [email protected] [email protected].
  7. Centre for Integrated Research into Musculoskeletal Ageing and Sheffield Healthy Lifespan Institute, University of Sheffield, Sheffield, UK.
  8. Institute for Translational Genomics, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany [email protected] [email protected].
  9. Translational Genomics, Klinikum rechts der Isar der Technischen Universitat Munchen, Munchen, Germany.

PMID: 33903094 PMCID: PMC8292595 DOI: 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

CONCLUSIONS: These data support the reproducible stratification of osteoarthritis patients by molecular subtype and the exploration of new avenues for tailored treatments.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: chondrocytes; inflammation; osteoarthritis

Conflict of interest statement

Competing interests: None declared.

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