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SAT0559 High Expression of Cyclooxygenase-2, Prostaglandin E2 and Prostaglandin E2 Receptor Ep4 in Zygapophyseal Joints of Patients with Ankylosing Spondylitis
  1. J. Bleil,
  2. H. Appel,
  3. R. Maier,
  4. J. Sieper,
  5. U. Syrbe
  1. Charité - Universitätsmedizin Berlin, Berlin, Germany

Abstract

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for patients with ankylosing spondylitis (AS). They are effective in reducing signs and symptoms, and increasing evidence suggests that their sustained use may also retard radiographic progression [1, 2]. The equal efficacy of cyclooxygenase (COX)-2 selective inhibitors in AS suggests that COX-2-dependent PGE2 synthesis is involved in the pathogenesis of AS.

Objectives We studied here the expression of COX-2 and PGE2 and of the PGE2 receptors EP2 and EP4 in zygapophyseal joints of AS patients.

Methods COX-2, PGE2, EP2 and EP4 were determined by immunohistochemistry in zygapophyseal joints from 19 AS, 11 osteoarthritis patients (OA) and 12 autopsy controls (CO). COX-2+, PGE+, EP+ and EP+ cells were detected at four different sites: within hyaline cartilage, subchondral bone plate, fibrous tissue and subchondral bone marrow.

Results Within the subchondral bone marrow, numbers of COX-2+ and PGE+ cells were higher in joints of AS patients compared to controls (p=0.0394, p=0.0138). The number of cells expressing EP2 and EP4 were also but non-significantly elevated in the bone marrow of AS patients (p=0.0630; p=0.0786). In contrast, we found in preliminary analysis very low expression of COX-2 within the cartilage, the subchondral bone and the subchondral fibrous tissue.

Within the subchondral bone plate, numbers of PGE+ and EP+ cells were higher in AS (and OA) patients compared to controls (p<0.05 for all), while no significant differences were seen within the cartilage comparing AS patients and controls.

Comparably very high numbers of PGE+ and EP+ cells were detected within the fibrous tissue of AS and OA patients (p=0.1902, p=0.3726).

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Conclusions According to these data, COX-2 dependent PGE2 synthesis is primarily seen in the subchondral bone marrow and elevated in AS patients, and might be the target site for drugs inhibiting COX-2.

References

  1. Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Annals of the rheumatic diseases. 2012 Oct; 71(10):1616-1622.

  2. Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis and rheumatism. 2005 Jun; 52(6):1756-1765.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3576

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