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From skeletal to cardiovascular disease in 12 steps—the evolution of sclerostin as a major player in CKD-MBD

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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 disease—the 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.

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Authors and Affiliations

  1. Department of Cardiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52057, Aachen, Germany

    Vincent M. Brandenburg & Annika Deck

  2. Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium

    Patrick D’Haese & Ellen Neven

  3. Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium

    Djalila Mekahli

  4. Department of Immunology and Microbiology, Laboratory of Nephrology, University Hospitals Leuven, Leuven, Belgium

    Björn Meijers & Pieter Evenepoel

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  1. Vincent M. Brandenburg
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Brandenburg, V.M., D’Haese, P., Deck, A. et al. From skeletal to cardiovascular disease in 12 steps—the evolution of sclerostin as a major player in CKD-MBD. Pediatr Nephrol 31, 195–206 (2016). https://doi.org/10.1007/s00467-015-3069-7

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