Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis

J Rheumatol. 2011 May;38(5):821-7. doi: 10.3899/jrheum.100089. Epub 2011 Mar 1.

Abstract

Objective: To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.

Methods: Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.

Results: The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10(-4)) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).

Conclusion: DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Bone Resorption / blood*
  • C-Reactive Protein / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation / blood*
  • Intercellular Signaling Peptides and Proteins / blood*
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Male
  • Middle Aged
  • Osteoprotegerin / blood
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin 1 Receptor Antagonist Protein
  • Osteoprotegerin
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein