title: Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease.
abstract: Renal osteodystrophy affects the majority of patients with advanced chronic kidney disease (CKD) and is characterized by progressive bone loss. This study evaluated the effects of sclerostin knockout on bone in a murine model of severe, surgically induced CKD in both sclerostin knockout and wild-type mice. Mice of both genotypes with normal kidney function served as controls. Tibiae were analyzed using micro-computed tomography, and lumbar vertebrae were analyzed by histomorphometry. Results were tested for statistical significance by 2-way ANOVA to investigate whether bone of the knockout mice reacted differently to CKD compared with bone of wild-type mice. In the tibiae, there was no difference after creation of CKD between wild-type and knockout animals for cortical thickness or cross-sectional moment of inertia. Increases in cortical porosity induced by CKD differed significantly between genotypes in the tibial metaphysis but not in the diaphysis. In the trabecular compartment, no difference in reaction to CKD between genotypes was found for bone volume, trabecular number, trabecular thickness, and trabecular separation. In the lumbar vertebrae, significant differences in response to CKD between wild-type and knockout mice were seen for both bone volume and trabecular thickness. Osteoblast parameters did not differ significantly, whereas osteoclast numbers significantly increased in the wild-type but significantly decreased in knockout mice with CKD. No differences in response to CKD between genotypes were found for bone formation rate or mineral apposition rate. Thus, complete absence of sclerostin has only minor effects on CKD-induced bone loss in mice.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria. Electronic address: daniel.cejka@meduniwien.ac.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cejka
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Diego
authors.initials: D
authors.lastname: Parada-Rodriguez
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Pichler
authors.affiliation: Department of Laboratory Medicine, Medical University Vienna, Austria.
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.affiliation: Muscoloskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Ina
authors.initials: I
authors.lastname: Kramer
authors.affiliation: Muscoloskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kneissel
authors.affiliation: Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gross
authors.affiliation: Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reisinger
authors.affiliation: Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Pahr
authors.affiliation: Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Monier-Faugere
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Haas
authors.affiliation: Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000166:cytology / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism; D013977:Tibia; D055114:X-Ray Microtomography
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse
keywords: bone; kidney disease; mouse; renal osteodystrophy; sclerostin