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Sost deficiency led to enhanced Dkk1 expression coincident with a greater cortical bone formation response to mechanical loading

Pflanz, David and Birkhold, Annette I. and Albiol, Laia and Thiele, Tobias and Duda, Georg and Checa, Sara and Willie, Bettina M. and Kornak, Uwe and Kneissel, Michaela and Kramer, Ina (2017) Sost deficiency led to enhanced Dkk1 expression coincident with a greater cortical bone formation response to mechanical loading. Scientific reports. ISSN 2045-2322

Abstract

Bone adaptation optimizes mass and structure, but the mechano-response is already reduced
at maturation. Downregulation of sclerostin was believed to be a mandatory step in mechanoadaptation,
but in young mice it was shown that load-induced formation can occur
independent of sclerostin, a product of the Sost gene. We hypothesized that the bone
formation and resorption response to loading is not affected by Sost deficiency, but is agespecific.
Our findings indicate that the anabolic response to in vivo tibial loading was reduced
at maturation in Sost Knockout (KO) and littermate control (LC) mice. Age affected all
anabolic and catabolic parameters and altered Sost and Wnt target gene expression. While
load-induced cortical resorption was similar between genotypes, loading-induced gains in
mineralizing surface was enhanced in Sost KO compared to LC mice. Loading led to a
downregulation in expression of the Wnt inhibitor Dkk1. Expression of Dkk1 was greater in
both control and loaded limbs of Sost KO compared to LC mice suggesting a compensatory
role in the absence of Sost. These data suggest physical activity could enhance bone mass
concurrently with sclerostin-neutralizing antibodies, but treatment strategies should consider
the influence of age on ultimate load-induced bone mass gains.

Item Type: Article
Date Deposited: 22 Feb 2017 00:45
Last Modified: 22 Feb 2017 00:45
URI: https://oak.novartis.com/id/eprint/29373

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