Publication
Title
Sclerostin as regulatory molecule in vascular media calcification and the bone–vascular axis
Author
Abstract
Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce vascular calcification. Vascular smooth muscle cell transdifferentiation, vascular calcification grade, and bone histomorphometry were examined. The presence and/or production of sclerostin was investigated in serum, aorta, and bone. Calcified human aortas were investigated to substantiate clinical relevance. Warfarin-exposed rats developed vascular calcifications in a time-dependent manner which went along with a progressive increase in serum sclerostin levels. Both osteogenic and adipogenic pathways were upregulated in calcifying vascular smooth muscle cells, as well as sclerostin mRNA and protein levels. Evidence for the local vascular action of sclerostin was found both in human and rat calcified aortas. Warfarin exposure led to a mildly decreased bone and mineralized areas. Osseous sclerostin production and bone turnover did not change significantly. This study showed local production of sclerostin in calcified vessels, which may indicate a negative feedback mechanism to prevent further calcification. Furthermore, increased levels of serum sclerostin, probably originating from excessive local production in calcified vessels, may contribute to the linkage between vascular pathology and impaired bone mineralization.
Language
English
Source (journal)
Toxins
Publication
2019
ISSN
2072-6651
DOI
10.3390/TOXINS11070428
Volume/pages
11 :7 (2019) , 15 p.
Article Reference
428
ISI
000482110000024
Pubmed ID
31330917
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
In vitro and in vivo research to investigate the role of the Wnt/betacatenin signalling cascade in the calcification paradox by targeting its most important inhibitors DKK1 and sclerostin.
In vitro and in vivo research to investigate the role of the Wnt/beta-catenin signaling cascade in vascular calcification and the bone-vascular axis.
INFLA-MED - Fundamental research in the pathophysiological processes of inflammatory diseases.
Arterial stiffening as a common pathophysiological mechanism in cardiac and kidney failure and brain degeneration.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 25.07.2019
Last edited 02.10.2024
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