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Arthritis Rheum. 2010 Jan;62(1):150-8. doi: 10.1002/art.27231.

Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis.

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  • 1Department of Internal Medicine, Division of Rheumatology, Patras University Hospital, University of Patras, Patras, Greece. jimdaoussis@hotmail.com

Abstract

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 alpha (anti-TNFalpha) 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-TNFalpha 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.

PMID:
20039407
[PubMed - indexed for MEDLINE]
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