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Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669501/ https://www.ncbi.nlm.nih.gov/pubmed/31330917 http://dx.doi.org/10.3390/toxins11070428 |
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author | De Maré, Annelies Maudsley, Stuart Azmi, Abdelkrim Hendrickx, Jhana O. Opdebeeck, Britt Neven, Ellen D’Haese, Patrick C Verhulst, Anja |
author_facet | De Maré, Annelies Maudsley, Stuart Azmi, Abdelkrim Hendrickx, Jhana O. Opdebeeck, Britt Neven, Ellen D’Haese, Patrick C Verhulst, Anja |
author_sort | De Maré, Annelies |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6669501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66695012019-08-08 Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis De Maré, Annelies Maudsley, Stuart Azmi, Abdelkrim Hendrickx, Jhana O. Opdebeeck, Britt Neven, Ellen D’Haese, Patrick C Verhulst, Anja Toxins (Basel) Article 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. MDPI 2019-07-21 /pmc/articles/PMC6669501/ /pubmed/31330917 http://dx.doi.org/10.3390/toxins11070428 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Maré, Annelies Maudsley, Stuart Azmi, Abdelkrim Hendrickx, Jhana O. Opdebeeck, Britt Neven, Ellen D’Haese, Patrick C Verhulst, Anja Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title | Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title_full | Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title_fullStr | Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title_full_unstemmed | Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title_short | Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis |
title_sort | sclerostin as regulatory molecule in vascular media calcification and the bone–vascular axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669501/ https://www.ncbi.nlm.nih.gov/pubmed/31330917 http://dx.doi.org/10.3390/toxins11070428 |
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