Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis
| Autor: | Andrew P. Andonopoulos, Georgios Yiannopoulos, Maria P. Karampetsou, Konstadina Bounia, Stamatis-Nick C. Liossis, Dimitrios Daoussis, Anastasia Tsanaktsi, Elena E. Solomou |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Health Status T cell Immunology Arthritis Severity of Illness Index Jurkat cells Receptors Tumor Necrosis Factor Etanercept Arthritis Rheumatoid Jurkat Cells Rheumatology Internal medicine Humans Immunology and Allergy Medicine Spondylitis Ankylosing Pharmacology (medical) Antibodies Blocking Ankylosing spondylitis biology Tumor Necrosis Factor-alpha business.industry Arthritis Psoriatic Wnt signaling pathway Antibodies Monoclonal Middle Aged medicine.disease Wnt Proteins Endocrinology medicine.anatomical_structure Immunoglobulin G Rheumatoid arthritis biology.protein Intercellular Signaling Peptides and Proteins Female Antibody business Signal Transduction medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 62:150-158 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.27231 |
| Popis: | Objective Dkk-1 is an inhibitory molecule that regulates the Wnt pathway, which controls osteoblastogenesis. This study was undertaken to explore the potential role of Dkk-1 in ankylosing spondylitis (AS), a prototypical bone-forming disease. Methods Serum Dkk-1 levels were measured in 45 patients with AS, 45 patients with rheumatoid arthritis (RA), 15 patients with psoriatic arthritis (PsA), and 50 healthy subjects by sandwich enzyme-linked immunosorbent assay (ELISA). A functional ELISA was used to assess the binding of Dkk-1 to its receptor (low-density lipoprotein receptor–related protein 6). Furthermore, we studied the effect of sera from patients with AS and healthy subjects on the activity of the Wnt pathway in the Jurkat T cell model, with and without a neutralizing anti–Dkk-1 monoclonal antibody, by Western immunoblotting. Results Serum Dkk-1 levels were significantly increased in patients with AS (mean ± SEM 2,730 ± 135.1 pg/ml) as compared with normal subjects (P = 0.040), patients with RA (P = 0.020), and patients with PsA (P = 0.049). Patients with AS receiving anti–tumor necrosis factor α (anti-TNFα) treatment had significantly higher serum Dkk-1 levels than patients with AS not receiving such treatment (P = 0.007). Patients with AS studied serially prior to and following anti-TNFα administration exhibited a significant increase in serum Dkk-1 levels (P = 0.020), in contrast to patients with RA, who exhibited a dramatic decrease (P < 0.001). Jurkat cells treated with serum from AS patients exhibited increased Wnt signaling compared with cells treated with control serum. In that system, Dkk-1 blockade significantly enhanced Wnt signaling in control serum–treated, but not AS serum–treated, Jurkat T cells. Conclusion Our findings indicate that in patients with AS, circulating bone formation–promoting factors functionally prevail. This can be at least partially attributed to decreased Dkk-1–mediated inhibition. |
| Databáze: | OpenAIRE |
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