IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-44053-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44053-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44053-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kathryn Weinand & Saori Sakaue & Aparna Nathan & Anna Helena Jonsson & Fan Zhang & Gerald F. M. Watts & Majd Al Suqri & Zhu Zhu & Deepak A. Rao & Jennifer H. Anolik & Michael B. Brenner & Laura T. Don, 2024. "The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    2. Meiling Zheng & Zhi Hu & Xiaole Mei & Lianlian Ouyang & Yang Song & Wenhui Zhou & Yi Kong & Ruifang Wu & Shijia Rao & Hai Long & Wei Shi & Hui Jing & Shuang Lu & Haijing Wu & Sujie Jia & Qianjin Lu & , 2022. "Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Alessandra Nerviani & Marie-Astrid Boutet & Giulia Maria Ghirardi & Katriona Goldmann & Elisabetta Sciacca & Felice Rivellese & Elena Pontarini & Edoardo Prediletto & Federico Abatecola & Mattia Calis, 2024. "Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Joyce B. Kang & Aparna Nathan & Kathryn Weinand & Fan Zhang & Nghia Millard & Laurie Rumker & D. Branch Moody & Ilya Korsunsky & Soumya Raychaudhuri, 2021. "Efficient and precise single-cell reference atlas mapping with Symphony," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    5. Ruiye Bi & Qing Yin & Haohan Li & Xianni Yang & Yiru Wang & Qianli Li & Han Fang & Peiran Li & Ping Lyu & Yi Fan & Binbin Ying & Songsong Zhu, 2023. "A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Samira Abbasgholizadeh Rahimi & Mojtaba Kolahdoozi & Arka Mitra & Jose L. Salmeron & Amir Mohammad Navali & Alireza Sadeghpour & Seyed Amir Mir Mohammadi, 2022. "Quantum-Inspired Interpretable AI-Empowered Decision Support System for Detection of Early-Stage Rheumatoid Arthritis in Primary Care Using Scarce Dataset," Mathematics, MDPI, vol. 10(3), pages 1-19, February.
    7. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Nabangshu Das & Luiz G. N. Almeida & Afshin Derakhshani & Daniel Young & Kobra Mehdinejadiani & Paul Salo & Alexander Rezansoff & Gregory D. Jay & Christian P. Sommerhoff & Tannin A. Schmidt & Roman K, 2023. "Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Michael T. H. Ng & Rowie Borst & Hamez Gacaferi & Sarah Davidson & Jessica E. Ackerman & Peter A. Johnson & Caio C. Machado & Ian Reekie & Moustafa Attar & Dylan Windell & Mariola Kurowska-Stolarska &, 2024. "A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    10. Niki Karagianni & Ksanthi Kranidioti & Nikolaos Fikas & Maria Tsochatzidou & Panagiotis Chouvardas & Maria C Denis & George Kollias & Christoforos Nikolaou, 2019. "An integrative transcriptome analysis framework for drug efficacy and similarity reveals drug-specific signatures of anti-TNF treatment in a mouse model of inflammatory polyarthritis," PLOS Computational Biology, Public Library of Science, vol. 15(5), pages 1-25, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44053-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.