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Sclerostin knock-out does not protect from uremia-induced bone loss in a murine model of chronic renal failure

Cejka, Daniel and Parada-Rodriguez, Diego and Pichler, Stefanie and Marculescu, Rodrig and Kramer, Ina and Kneissel, Michaela and Gross, Thomas and Reisinger, Andreas and Pahr, Dieter and Monier-Faugere, Marie-Claude and Haas, Martin and Malluche, Hartmut H. (2016) Sclerostin knock-out does not protect from uremia-induced bone loss in a murine model of chronic renal failure. Kidney International.

Abstract

Renal osteodystrophy affects the majority of patients with advanced chronic kidney disease (CKD) and is characterized by progressive bone loss. This study evaluates the effects of sclerostin knock-out on bone in a murine model of CKD.
Severe CKD was surgically induced in sclerostin knock-out (SOST-KO-CKD) and wild-type (WT-CKD) mice. Mice with normal kidney function served as controls (SOST-KO-CTRL, WT-CTRL). Tibiae were analyzed using micro-computed tomography (µCT). Lumbar vertebrae were analyzed by histomorphometry. Results were tested for statistical significance by two-way ANOVA to investigate whether bone of SOST-KO mice reacted differently to CKD compared to bone of WT mice.
In the tibiae there was no difference in reaction to CKD between WT and SOST-KO for cortical thickness or cross-sectional moment of inertia (CSMI). Increases in cortical porosity induced by CKD differed significantly between genotypes in the tibial epiphysis (p<0.005) but not in the diaphysis (p=0.7). 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, differences in response to CKD between WT and SOST-KO were seen for bone volume (p<0.01) and trabecular thickness (p<0.001). Osteoblast parameters did not differ significantly, whereas osteoclast numbers increased in WT-CKD but decreased in SOST-KO-CKD (p<0.01). No differences in response to CKD between genotypes were found for bone formation rate (BFR/BS) or mineral apposition rate (MAR).
In conclusion, sclerostin knock-out does not protect from uremia-induced bone loss in mice after subtotal nephrectomy.

Item Type: Article
Date Deposited: 22 Apr 2016 23:45
Last Modified: 22 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/27473

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