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Supplementary Data S2 from <i>Sost</i> deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched <i>in vivo</i> loading experiments in mice

By Laia Albiol (680055), Myriam Cilla (4413073), David Pflanz (5039834), Ina Kramer (5039831), Michaela Kneissel (2312887), Georg N. Duda (108610), Bettina M. Willie (805637) and Sara Checa (4413067)

Abstract

Sclerostin, a product of the <i>Sost</i> gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. <i>Sost</i> knockout (KO) mice were examined to gain insight on how long-term <i>Sost</i> deficiency alters the local mechanical environment within the bone. This knowledge is crucial since the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult <i>Sost</i> KO and age-matched littermate control (LC) mice using microcomputed tomography imaging. The cortical area and the minimal and maximal moment of inertia were higher in <i>Sost</i> KO than in LC mice, whereas no difference was detected in either the anterior–posterior or medio-lateral bone curvature. Differences observed between age-matched genotypes were greater in adult mice. We analysed the local mechanical environment in the bone using finite-element models (FEMs), which showed that strains in the tibiae of <i>Sost</i> KO mice are lower than in age-matched LC mice at the diaphyseal midshaft, a region commonly used to assess cortical bone formation and resorption. Our FEMs also suggested that tissue mineral density is only a minor contributor to the strain distribution in tibial cortical bone from <i>Sost</i> KO mice compared to bone geometry. Furthermore, they indicated that although strain gauging experiments matched strains at the gauge site, strains along the tibial length were not comparable between age-matched <i>Sost</i> KO and LC mice or between young and adult animals within the same genotype

Topics: Biomechanics, Sost, sclerostin, maturation, mechanical strain, finite-element analysis
Year: 2018
DOI identifier: 10.6084/m9.figshare.6063308.v1
OAI identifier: oai:figshare.com:article/6063308
Provided by: FigShare
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