title: Sclerostin and DKK1: new players in renal bone and vascular disease.
abstract: For more than a decade, the Wnt-β-catenin pathway has been the focus of intense basic and clinical research in the bone field because of its importance in skeletal development and maintenance of bone mass. Wnt activation increases bone formation and decreases bone resorption. The Wnt-β-catenin signaling pathway is tightly regulated by several inhibitors, among which Dickkopf-related protein 1 (DKK1) and sclerostin have been most comprehensively studied. Mounting evidence indicates that a disturbed Wnt-β-catenin signaling is also implicated in the pathogenesis of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD) and affects its various components. DKK1 and sclerostin, more specifically, may be involved in the intense cross-talk between the kidneys, vasculature, and bone. Studies exploring clinical correlates of circulating sclerostin and DKK1 levels so far yielded conflicting results. Biological variability and analytical issues account at least partly for this inconsistency. Antibodies neutralizing Wnt inhibitors may be an appealing strategy to prevent or treat CKD-MBD. Caution is however warranted as sclerostin not only opposes mineralization in the bone but possibly also in the vasculature. Additional studies are required to define determinants of Wnt inhibitors in CKD and to evaluate the efficacy and safety of recently introduced pharmaceuticals targeting these inhibitors.
authors.affiliation: Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, and Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, Antwerp University, Wilrijk, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: D'Haese
authors.affiliation: Department of Cardiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Brandenburg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001847:Bone Diseases / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001862:Bone Resorption; D002114:Calcinosis / Q000097:blood*; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D010012:Osteogenesis; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D014652:Vascular Diseases / Q000097:blood*; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human