bone turnover; chronic kidney disease (CKD); osteocyte; parathyroid hormone (PTH); parathyroidectomy (PTX); renal osteodystrophy (ROD); sclerostin; Parathyroid Hormone; Rats; Animals; Osteocytes/metabolism; Bone and Bones/metabolism; Bone Remodeling; Parathyroid Hormone/metabolism; Chronic Kidney Disease-Mineral and Bone Disorder/metabolism; Renal Insufficiency, Chronic/complications; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Osteocytes; Renal Insufficiency, Chronic; Food Science; Nutrition and Dietetics
Abstract :
[en] Renal osteodystrophy (ROD) is a complex and serious complication of chronic kidney disease (CKD), a major global health problem caused by loss of renal function. Currently, the gold standard to accurately diagnose ROD is based on quantitative histomorphometric analysis of trabecular bone. Although this analysis encompasses the evaluation of osteoblast and osteoclast number/activity, tfigurehe interest in osteocytes remains almost nihil. Nevertheless, this cell type is evidenced to perform a key role in bone turnover, particularly through its production of various bone proteins, such as sclerostin. In this study, we aim to investigate, in the context of ROD, to which extent an association exists between bone turnover and the abundance of osteocytes and osteocytic sclerostin expression in both the trabecular and cortical bone compartments. Additionally, the effect of parathyroid hormone (PTH) on bone sclerostin expression was examined in parathyroidectomized rats. Our results indicate that PTH exerts a direct inhibitory function on sclerostin, which in turn negatively affects bone turnover and mineralization. Moreover, this study emphasizes the functional differences between cortical and trabecular bone, as the number of (sclerostin-positive) osteocytes is dependent on the respective bone compartment. Finally, we evaluated the potential of sclerostin as a marker for CKD and found that the diagnostic performance of circulating sclerostin is limited and that changes in skeletal sclerostin expression occur more rapidly and more pronounced. The inclusion of osteocytic sclerostin expression and cortical bone analysis could be relevant when performing bone histomorphometric analysis for diagnostic purposes and to unravel pathological mechanisms of bone disease.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Huybrechts, Yentl; Laboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, Belgium ; Center of Medical Genetics, University of Antwerp, 2650 Antwerp, Belgium
Evenepoel, Pieter; Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, 3000 Leuven, Belgium
Haarhaus, Mathias ; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, 141 52 Stockholm, Sweden ; Diaverum AB, 215 37 Malmö, Sweden
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Dams, Geert; Laboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, Belgium
Van Hul, Wim ; Center of Medical Genetics, University of Antwerp, 2650 Antwerp, Belgium
D'Haese, Patrick C ; Laboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, Belgium
Verhulst, Anja ; Laboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, Belgium
Language :
English
Title :
Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover.
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