Options
Sost deficiency led to a greater cortical bone formation response to mechanical loading and altered gene expression
Publikationstyp
Journal Article
Date Issued
2017-12-01
Sprache
English
Author(s)
Pflanz, David
Birkhold, Annette I.
Albiol, Laia
Thiele, Tobias
Julien, Catherine
Seliger, Anne
Thomson, Erin
Kramer, Ina
Kneissel, Michaela
Kornak, Uwe
Journal
Volume
7
Issue
1
Article Number
9435
Citation
Scientific Reports 7 (1): 9435
Publisher DOI
Scopus ID
Publisher
Nature Publishing Group
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 mechano-adaptation, 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 age-specific. 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.
DDC Class
610: Medicine, Health