The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis
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Published:2023-12-09
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Elhai MurielORCID, Micheroli RaphaelORCID, Houtman Miranda, Mirrahimi Masoumeh, Moser Larissa, Pauli Chantal, Bürki Kristina, Laimbacher Andrea, Kania GabrielaORCID, Klein KerstinORCID, Schätzle Philipp, Bertoncelj Mojca Frank, Edalat Sam G., Keusch Leandra, Khmelevskaya Alexandra, Toitou MelpomeniORCID, Geiss CelinaORCID, Rauer ThomasORCID, Sakkou Maria, Kollias GeorgeORCID, Armaka MariettaORCID, Distler OliverORCID, Ospelt CarolineORCID
Abstract
AbstractAlthough 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference93 articles.
1. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 392, 1789–1858 (2018). 2. Bijlsma, J. W. J. et al. EULAR textbook on rheumatic diseases. BMJ Publishing Group United Kingdom (2018). 3. van der Woude, D. van der Helm-van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best practice & research. Clin. Rheumatol. 32, 174–187 (2018). 4. Buch, M. H., Eyre, S. & McGonagle, D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat. Rev. Rheumatol. 17, 17–33 (2021). 5. Ciurea, A. et al. Joint-level responses to tofacitinib and methotrexate: a post hoc analysis of data from ORAL Start. Arthr. Res. Ther. 25, 185 (2023).
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