Title
From skeletal to cardiovascular disease in 12 steps : the evolution of sclerostin as a major player in CKD-MBD From skeletal to cardiovascular disease in 12 steps : the evolution of sclerostin as a major player in CKD-MBD
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Berlin ,
Subject
Human medicine
Source (journal)
Pediatric nephrology. - Berlin
Volume/pages
31(2016) :2 , p. 195-206
ISSN
0931-041X
ISI
000367457800004
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization and is an essential player in bone remodeling. Sclerostin is a prototypic soluble canonical Wnt signaling pathway inhibitor that is produced in osteocytes and blocks osteoblast differentiation and function. Therefore, sclerostin is a potent inhibitor of bone formation and mineralization. Accordingly, rodent sclerostin-deficiency models exhibit a strong bone phenotype. Moreover, blocking sclerostin represents a promising treatment perspective against osteoporosis. Beyond the bone field novel data definitely associate Wnt signaling in general and sclerostin in particular with ectopic extraosseous mineralization processes, as is evident in cardiovascular calcification or calciphylaxis. Uremia is characterized by parallel occurrence of disordered bone mineralization and accelerated cardiovascular calcification (chronic kidney disease mineral and bone disorder, CKD-MBD), linking skeletal and cardiovascular diseasethe so-called bone-vascular calcification paradox. In consequence, sclerostin may qualify as an emerging player in CKD-MBD. We present a stepwise review approach regarding the rapidly evolving field sclerostin participation in CKD-MBD. Starting from data originating in the classical bone field we look separately at three major areas of CKD-MBD: disturbed mineral metabolism, renal osteodystrophy, and uremic cardiovascular disease. Our review is intended to help the nephrologist revise the potential importance of sclerostin in CKD by focusing on how sclerostin research is gradually evolving from the classical osteoporosis niche into the area of CKD-MBD. In particular, we integrate the limited amount of available data in the context of pediatric nephrology.
E-info
https://repository.uantwerpen.be/docman/iruaauth/2831e3/137da54df32.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/058892/9791.pdf
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