TY - JOUR
T1 - Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression
AU - Mauro, Daniele
AU - Srinath, Archita
AU - Guggino, Giuliana
AU - Nicolaidou, Vicky
AU - Raimondo, Stefania
AU - Ellis, Jonathan J.
AU - Whyte, Jessica
AU - Nicoletti, Maria Maddalena
AU - Romano, Marco
AU - Kenna, Tony John
AU - Cañete, Juan D.
AU - Alessandro, Riccardo
AU - Rizzo, Aroldo
AU - Brown, Matthew Arthur
AU - Horwood, Nicole J.
AU - Haroon, Nigil
AU - Ciccia, Francesco
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Ankylosing spondylitis
KW - EP4
KW - Monocytes
KW - Prostaglandins
KW - PTGER4
KW - Radiographic progression
UR - http://www.scopus.com/inward/record.url?scp=85153611938&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2023.109332
DO - 10.1016/j.clim.2023.109332
M3 - Article
C2 - 37075950
AN - SCOPUS:85153611938
SN - 1521-6616
VL - 251
JO - Clinical Immunology
JF - Clinical Immunology
M1 - 109332
ER -