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

Daniele Mauro, Archita Srinath, Giuliana Guggino, Vicky Nicolaidou, Stefania Raimondo, Jonathan J. Ellis, Jessica Whyte, Maria Maddalena Nicoletti, Marco Romano, Tony John Kenna, Juan D. Cañete, Riccardo Alessandro, Aroldo Rizzo, Matthew Arthur Brown, Nicole J. Horwood, Nigil Haroon, Francesco Ciccia

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number109332
JournalClinical Immunology
Volume251
Early online date17 Apr 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Ankylosing spondylitis
  • EP4
  • Monocytes
  • Prostaglandins
  • PTGER4
  • Radiographic progression

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