Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression

Mauro, Daniele, Srinath, Archita, Guggino, Giuliana, Nicolaidou, Vicky, Raimondo, Stefania, Ellis, Jonathan J., Whyte, Jessica, Nicoletti, Maria Maddalena, Romano, Marco, Kenna, Tony John, Cañete, Juan D., Alessandro, Riccardo, Rizzo, Aroldo, Brown, Matthew Arthur, Horwood, Nicole J. ORCID:, Haroon, Nigil and Ciccia, Francesco (2023) Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression. Clinical Immunology, 251. ISSN 1521-6616

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Ankylosing spondylitis (AS) is an inflammatory disease leading to spine ankylosis; however, the mechanisms behind new bone formation are still not fully understood. Single Nucleotide Polymorphisms (SNPs) in PTGER4, encoding for the receptor EP4 of prostaglandin E2 (PGE2), are associated with AS. Since the PGE2-EP4 axis participates in inflammation and bone metabolism, this work aims at investigating the influence of the prostaglandin-E2 axis on radiographic progression in AS. In 185 AS (97 progressors), baseline serum PGE2 predicted progression, and PTGER4 SNP rs6896969 was more frequent in progressors. Increased EP4/PTGER4 expression was observed in AS circulating immune cells, synovial tissue, and bone marrow. CD14highEP4 + cells frequency correlated with disease activity, and when monocytes were cocultured with mesenchymal stem cells, the PGE2/EP4 axis induced bone formation. In conclusion, the Prostaglandin E2 axis is involved in bone remodelling and may contribute to the radiographic progression in AS due to genetic and environmental upregulation.

Item Type: Article
Additional Information: Funding Information: We thank the physicians who facilitate sample collection and the patients and controls participating in the study. Publisher Copyright: © 2023
Uncontrolled Keywords: ankylosing spondylitis,ep4,monocytes,prostaglandins,ptger4,radiographic progression,immunology and allergy,immunology ,/dk/atira/pure/subjectarea/asjc/2700/2723
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 22 Jun 2023 09:31
Last Modified: 19 Oct 2023 03:36
DOI: 10.1016/j.clim.2023.109332

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