title: Circulating Wnt/β-catenin signalling inhibitors and uraemic vascular calcifications.
abstract: BACKGROUND
  The process of vascular calcification has been associated with the canonical Wnt/β-catenin signalling pathway in cell cultures and animal studies. The relationship between circulating Wnt/β-catenin inhibitors and vascular calcification in dialysis patients is unknown. The aim of this study was to investigate the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signalling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in dialysis patients.
  
  
  METHODS
  This was a prospective observational cohort study. One hundred and twenty-five patients on maintenance haemodialysis participated in the study. Serum levels of Dkk-1 and sclerostin were measured. AoC scores were calculated from plain films of both posterior-anterior and lateral views. The patients were followed up for 2 years or until death or withdrawal.
  
  
  RESULTS
  The circulating sclerostin level was inversely associated with the severity of AoC (P = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, P = 0.008) and intact parathyroid hormone (r = -0.523, P < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), P = 0.015] after adjusting for a propensity score. In contrast, serum Dkk-1 was not associated with AoC and clinical outcomes.
  
  
  CONCLUSIONS
  In long-term haemodialysis patients, circulating sclerostin but not Dkk-1 is inversely associated with AoCs and future cardiovascular events. Our findings suggest that sclerostin, as a bone-related protein, might act as a communicator between uraemic bone and vasculature.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Chih-Yu
authors: CY
authors: Yang
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: Zee-Fen
authors: ZF
authors: Chang
authors: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors: Yat-Pang
authors: YP
authors: Chau
authors: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Ann
authors: A
authors: Chen
authors: School of Medicine, National Yang-Ming University, Taipei, Taiwan Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Wu-Chang
authors: WC
authors: Yang
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: An-Hang
authors: AH
authors: Yang
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan Department of Orthopedic Surgery, Taipei City Hospital, Taipei, Taiwan.
authors: Oscar Kuang-Sheng
authors: OK
authors: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000097:blood* / Q000209:etiology; D061205:Vascular Calcification / Q000097:blood* / Q000209:etiology; D060449:Wnt Signaling Pathway
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; D010281:Parathyroid Hormone; C422903:SOST protein, human
keywords: aortic calcification; dickkopf-1; outcome; sclerostin; uraemia