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The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis

Author

Listed:
  • Muriel Elhai

    (University Hospital of Zurich, University of Zurich)

  • Raphael Micheroli

    (University Hospital of Zurich, University of Zurich)

  • Miranda Houtman

    (University Hospital of Zurich, University of Zurich)

  • Masoumeh Mirrahimi

    (University Hospital of Zurich, University of Zurich)

  • Larissa Moser

    (University Hospital of Zurich, University of Zurich)

  • Chantal Pauli

    (University Hospital Zurich)

  • Kristina Bürki

    (University Hospital of Zurich, University of Zurich)

  • Andrea Laimbacher

    (University Hospital of Zurich, University of Zurich)

  • Gabriela Kania

    (University Hospital of Zurich, University of Zurich)

  • Kerstin Klein

    (University Hospital of Zurich, University of Zurich
    University of Bern
    Inselspital, Bern University Hospital, University of Bern)

  • Philipp Schätzle

    (University of Zurich)

  • Mojca Frank Bertoncelj

    (University Hospital of Zurich, University of Zurich)

  • Sam G. Edalat

    (University Hospital of Zurich, University of Zurich)

  • Leandra Keusch

    (University Hospital of Zurich, University of Zurich)

  • Alexandra Khmelevskaya

    (University Hospital of Zurich, University of Zurich)

  • Melpomeni Toitou

    (University Hospital of Zurich, University of Zurich)

  • Celina Geiss

    (University Hospital of Zurich, University of Zurich)

  • Thomas Rauer

    (University Hospital Zurich)

  • Maria Sakkou

    (Biomedical Sciences Research Center (BSRC) ‘Alexander Fleming’
    Medical School, National and Kapodistrian University of Athens)

  • George Kollias

    (Biomedical Sciences Research Center (BSRC) ‘Alexander Fleming’
    Medical School, National and Kapodistrian University of Athens)

  • Marietta Armaka

    (Biomedical Sciences Research Center “Alexander Fleming”)

  • Oliver Distler

    (University Hospital of Zurich, University of Zurich)

  • Caroline Ospelt

    (University Hospital of Zurich, University of Zurich)

Abstract

Although patients with rheumatoid arthritis (RA) typically exhibit symmetrical joint involvement, some patients develop alternative disease patterns in response to treatment, suggesting that different molecular mechanism may underlie disease progression depending on joint location. Here, we identify joint-specific changes in RA synovium and synovial fibroblasts (SF) between knee and hand joints. We show that the long non-coding RNA HOTAIR, which is only expressed in knee SF, regulates more than 50% of this site-specific gene expression in SF. HOTAIR is downregulated after stimulation with pro-inflammatory cytokines and is expressed at lower levels in knee samples from patients with RA, compared with osteoarthritis. Knockdown of HOTAIR in knee SF increases PI-Akt signalling and IL-6 production, but reduces Wnt signalling. Silencing HOTAIR inhibits the migratory function of SF, decreases SF-mediated osteoclastogenesis, and increases the recruitment of B cells by SF. We propose that HOTAIR is an important epigenetic factor in joint-specific gene expression in RA.

Suggested Citation

  • Muriel Elhai & Raphael Micheroli & Miranda Houtman & Masoumeh Mirrahimi & Larissa Moser & Chantal Pauli & Kristina Bürki & Andrea Laimbacher & Gabriela Kania & Kerstin Klein & Philipp Schätzle & Mojca, 2023. "The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44053-w
    DOI: 10.1038/s41467-023-44053-w
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    1. Fumitaka Mizoguchi & Kamil Slowikowski & Kevin Wei & Jennifer L. Marshall & Deepak A. Rao & Sook Kyung Chang & Hung N. Nguyen & Erika H. Noss & Jason D. Turner & Brandon E. Earp & Philip E. Blazar & J, 2018. "Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    2. Kevin Wei & Ilya Korsunsky & Jennifer L. Marshall & Anqi Gao & Gerald F. M. Watts & Triin Major & Adam P. Croft & Jordan Watts & Philip E. Blazar & Jeffrey K. Lange & Thomas S. Thornhill & Andrew File, 2020. "Notch signalling drives synovial fibroblast identity and arthritis pathology," Nature, Nature, vol. 582(7811), pages 259-264, June.
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