title: High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis.
abstract: BACKGROUND
  The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS.
  
  
  METHODS
  This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels.
  
  
  RESULTS
  Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78 ± 5.48 pg/ml) compared with those with syndesmophyte growth (4.13 ± 2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI -0.10 to 0.38; p=0.23).
  
  
  CONCLUSIONS
  AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS.
authors.affiliation: Department of Internal Medicine III, University of Erlangen–Nuremberg, Germany.
authors.forename: Gisela Ruiz
authors.initials: GR
authors.lastname: Heiland
authors.forename: Heiner
authors.initials: H
authors.lastname: Appel
authors.forename: Denis
authors.initials: D
authors.lastname: Poddubnyy
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Axel
authors.initials: A
authors.lastname: Hueber
authors.forename: Hildrun
authors.initials: H
authors.lastname: Haibel
authors.forename: Xenofon
authors.initials: X
authors.lastname: Baraliakos
authors.forename: Joachim
authors.initials: J
authors.lastname: Listing
authors.forename: Martin
authors.initials: M
authors.lastname: Rudwaleit
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D054850:Osteophyte / Q000097:blood / Q000209:etiology*; D011379:Prognosis; D011859:Radiography; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human; D002097:C-Reactive Protein