000150478 001__ 150478
000150478 005__ 20251017144548.0
000150478 0247_ $$2doi$$a10.1098/rsif.2018.0012
000150478 0248_ $$2sideral$$a105828
000150478 037__ $$aART-2018-105828
000150478 041__ $$aeng
000150478 100__ $$aAlbiol, L.
000150478 245__ $$aSost deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched in vivo loading experiments in mice
000150478 260__ $$c2018
000150478 5060_ $$aAccess copy available to the general public$$fUnrestricted
000150478 5203_ $$aSclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/b-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. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone. This knowledge is crucial as the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult Sost 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 Sost 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 Sost 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 Sost 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 agematched Sost KO and LC mice or between young and adult animals within the same genotype.
000150478 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000150478 590__ $$a3.224$$b2018
000150478 591__ $$aMULTIDISCIPLINARY SCIENCES$$b14 / 68 = 0.206$$c2018$$dQ1$$eT1
000150478 592__ $$a1.627$$b2018
000150478 593__ $$aBiochemistry$$c2018$$dQ1
000150478 593__ $$aBioengineering$$c2018$$dQ1
000150478 593__ $$aBiotechnology$$c2018$$dQ1
000150478 593__ $$aBiomedical Engineering$$c2018$$dQ1
000150478 593__ $$aBiophysics$$c2018$$dQ1
000150478 593__ $$aBiomaterials$$c2018$$dQ1
000150478 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000150478 700__ $$0(orcid)0000-0002-8503-9291$$aCilla, M.
000150478 700__ $$aPflanz, D.
000150478 700__ $$aKramer, I.
000150478 700__ $$aKneissel, M.
000150478 700__ $$aDuda, G.N.
000150478 700__ $$aWillie, B.M.
000150478 700__ $$aCheca, S.
000150478 773__ $$g15, 141 (2018), 20180012$$pJ. R. Soc. Interface$$tJournal of the Royal Society Interface$$x1742-5689
000150478 8564_ $$s8446233$$uhttps://zaguan.unizar.es/record/150478/files/texto_completo.pdf$$yPostprint
000150478 8564_ $$s2381171$$uhttps://zaguan.unizar.es/record/150478/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000150478 909CO $$ooai:zaguan.unizar.es:150478$$particulos$$pdriver
000150478 951__ $$a2025-10-17-14:10:49
000150478 980__ $$aARTICLE