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Sclerostin, a 22-kDa glycoprotein that is mainly secreted by the osteocytes, is a soluble inhibitor of canonical Wnt signaling. Therefore, when present at increased concentrations, it leads to an increased bone resorption and decreased bone formation. Serum sclerostin levels are known to be increased in the elderly and in patients with chronic kidney disease. In these patient populations, there is a high incidence of ectopic cardiovascular calcification. These calcifications are strongly associated with cardiovascular morbidity and mortality. Although data are still controversial, it is likely that there is a link between ectopic calcification and serum sclerostin levels. The main question, however, remains whether sclerostin exerts either a protective or deleterious role in the ectopic calcification process.
Annelies De Maré; Patrick C. D’Haese; Anja Verhulst. The Role of Sclerostin in Bone and Ectopic Calcification. International Journal of Molecular Sciences 2020, 21, 3199 .
AMA StyleAnnelies De Maré, Patrick C. D’Haese, Anja Verhulst. The Role of Sclerostin in Bone and Ectopic Calcification. International Journal of Molecular Sciences. 2020; 21 (9):3199.
Chicago/Turabian StyleAnnelies De Maré; Patrick C. D’Haese; Anja Verhulst. 2020. "The Role of Sclerostin in Bone and Ectopic Calcification." International Journal of Molecular Sciences 21, no. 9: 3199.
Mounting evidence indicates that sclerostin, a well-known inhibitor of bone formation, may qualify as a clinically relevant biomarker of chronic kidney disease-related mineral and bone disorder (CKD-MBD), including abnormal mineral and bone metabolism and extraskeletal calcification. For this purpose, in this study we investigate the extent to which circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters, and serum markers of bone metabolism associate with each other. Bone biopsies and serum samples were collected in a cohort of 68 end-stage kidney disease (ESKD) patients. Serum sclerostin levels were measured using 4 different commercially available assays. Skeletal sclerostin expression was evaluated on immunohistochemically stained bone sections. Quantitative bone histomorphometry was performed on Goldner stained tissue sections. Different serum markers of bone metabolism were analyzed using in-house techniques or commercially available assays. Despite large inter-assay differences for circulating sclerostin, results obtained with the 4 assays under study closely correlated with each other, whilst moderate significant correlations with skeletal sclerostin expression were also found. Both skeletal and circulating sclerostin negatively correlated with histomorphometric bone and serum parameters reflecting bone formation and turnover. In this study, the unique combined evaluation of bone sclerostin expression, bone histomorphometry, bone biomarkers, and serum sclerostin levels, as assessed by 4 different assays, demonstrated that sclerostin may qualify as a clinically relevant marker of disturbed bone metabolism in ESKD patients.
Annelies De Maré; Anja Verhulst; Etienne Cavalier; Pierre Delanaye; Geert J. Behets; Bjorn Meijers; Dirk Kuypers; Patrick C. D’Haese; Pieter Evenepoel; Maré; D’ Haese. Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease. Journal of Clinical Medicine 2019, 8, 2027 .
AMA StyleAnnelies De Maré, Anja Verhulst, Etienne Cavalier, Pierre Delanaye, Geert J. Behets, Bjorn Meijers, Dirk Kuypers, Patrick C. D’Haese, Pieter Evenepoel, Maré, D’ Haese. Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease. Journal of Clinical Medicine. 2019; 8 (12):2027.
Chicago/Turabian StyleAnnelies De Maré; Anja Verhulst; Etienne Cavalier; Pierre Delanaye; Geert J. Behets; Bjorn Meijers; Dirk Kuypers; Patrick C. D’Haese; Pieter Evenepoel; Maré; D’ Haese. 2019. "Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease." Journal of Clinical Medicine 8, no. 12: 2027.
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.
Annelies De Maré; Stuart Maudsley; Abdelkrim Azmi; Jhana O. Hendrickx; Britt Opdebeeck; Ellen Neven; Patrick C D’Haese; Anja Verhulst. Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone-Vascular Axis. Toxins 2019, 11, 428 .
AMA StyleAnnelies De Maré, Stuart Maudsley, Abdelkrim Azmi, Jhana O. Hendrickx, Britt Opdebeeck, Ellen Neven, Patrick C D’Haese, Anja Verhulst. Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone-Vascular Axis. Toxins. 2019; 11 (7):428.
Chicago/Turabian StyleAnnelies De Maré; Stuart Maudsley; Abdelkrim Azmi; Jhana O. Hendrickx; Britt Opdebeeck; Ellen Neven; Patrick C D’Haese; Anja Verhulst. 2019. "Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone-Vascular Axis." Toxins 11, no. 7: 428.