前列腺素 E2/EP4 轴在脊柱关节炎中上调，并导致影像学进展。
Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression.
机构信息
Rheumatology Unit, Department of Precision Medicine, Università degli Studi della Campania "L. Vanvitelli", Naples, Italy.
Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
出版信息
Clin Immunol. 2023 Jun;251:109332. doi: 10.1016/j.clim.2023.109332. Epub 2023 Apr 17.
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.
强直性脊柱炎（AS）是一种导致脊柱强直的炎症性疾病，但新骨形成的机制仍不完全清楚。编码前列腺素 E2（PGE2）受体 EP4 的前列腺素 E 受体 4（PTGER4）中的单核苷酸多态性（SNP）与 AS 相关。由于 PGE2-EP4 轴参与炎症和骨代谢，本研究旨在探讨前列腺素-E2 轴对 AS 放射学进展的影响。在 185 例 AS 患者（97 例进展者）中，基线血清 PGE2 可预测进展，且 PTGER4 SNP rs6896969 在进展者中更为常见。在 AS 循环免疫细胞、滑膜组织和骨髓中观察到 EP4/PTGER4 表达增加。CD14highEP4+细胞频率与疾病活动度相关，当单核细胞与间充质干细胞共培养时，PGE2/EP4 轴诱导骨形成。总之，前列腺素 E2 轴参与骨重塑，并且由于遗传和环境的上调，可能导致 AS 的放射学进展。
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