前列腺素E2
医学
骨重建
下调和上调
前列腺素E2受体
间充质干细胞
骨髓
癌症研究
内科学
免疫学
病理
受体
生物
生物化学
基因
兴奋剂
作者
Daniele Mauro,Archita Srinath,Giuliana Guggino,Vicky Nicolaidou,Stefania Raimondo,Jonathan J. Ellis,Jessica M. Whyte,Maria Maddalena Nicoletti,Marco Romano,Tony John Kenna,Juan Cañete,Riccardo Alessandro,Aroldo Rizzo,Matthew Arthur Brown,Nicole J. Horwood,Nigil Haroon,Francesco Ciccia
标识
DOI:10.1016/j.clim.2023.109332
摘要
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.
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