Next Article in Journal
Aflatoxin in Chili Peppers in Nigeria: Extent of Contamination and Control Using Atoxigenic Aspergillus flavus Genotypes as Biocontrol Agents
Next Article in Special Issue
Modifying Phosphate Toxicity in Chronic Kidney Disease
Previous Article in Journal
Pain and Lethality Induced by Insect Stings: An Exploratory and Correlational Study
Previous Article in Special Issue
The Key Role of Phosphate on Vascular Calcification
Open AccessArticle

Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis

1
Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium
2
Receptor Biology Lab, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium
3
Translational Neurobiology Group, VIB Center for Molecular Neurology, University of Antwerp, 2610 Wilrijk, Belgium
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(7), 428; https://doi.org/10.3390/toxins11070428
Received: 29 June 2019 / Revised: 16 July 2019 / Accepted: 18 July 2019 / Published: 21 July 2019
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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. View Full-Text
Keywords: chronic kidney disease; vascular calcification; bone disease; mineral abnormalities; rat model chronic kidney disease; vascular calcification; bone disease; mineral abnormalities; rat model
Show Figures

Figure 1

MDPI and ACS Style

De Maré, A.; Maudsley, S.; Azmi, A.; Hendrickx, J.O.; Opdebeeck, B.; Neven, E.; D’Haese, P.C.; Verhulst, A. Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis. Toxins 2019, 11, 428.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop