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

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. •PGE2 serum level predicts radiographic progression in Ankylosing Spondylitis.•EP4 is upregulated in AS by genetic and environmental factors.•PGE2/EP4 axis is upregulated in AS in synovial tissue, bone marrow and peripheral blood.•EP4+ circulating monocytes are increased in AS and correlated with disease activity and smoking.•PGE2/EP4 axis modulated monocyte-induced bone formation in MSCs.