000136291 001__ 136291
000136291 005__ 20240731105612.0
000136291 0247_ $$2doi$$a10.1016/j.mbplus.2024.100155
000136291 0248_ $$2sideral$$a139255
000136291 037__ $$aART-2024-139255
000136291 041__ $$aeng
000136291 100__ $$aZimmermann, Elizabeth A.
000136291 245__ $$aTissue material properties, whole-bone morphology and mechanical behavior in the Fbn1C1041G/+ mouse model of Marfan syndrome
000136291 260__ $$c2024
000136291 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136291 5203_ $$aMarfan syndrome (MFS) is a connective tissue disorder caused by pathogenic mutations in FBN1. In bone, the protein fibrillin-1 is found in the extracellular matrix where it provides structural support of elastic fiber formation, stability for basement membrane, and regulates the bioavailability of growth factors. Individuals with MFS exhibit a range of skeletal complications including low bone mineral density and long bone overgrowth. However, it remains unknown if the bone phenotype is caused by alteration of fibrillin-1′s structural function or distortion of its interactions with bone cells. To assess the structural effects of the fibrillin-1 mutation, we characterized bone curvature, microarchitecture, composition, porosity, and mechanical behavior in the Fbn1C1041G/+ mouse model of MFS. Tibiae of 10, 26, and 52-week-old female Fbn1C1041G/+ and littermate control (LC) mice were analyzed. Mechanical behavior was assessed via in vivo strain gauging, finite element analysis, ex vivo three-point bending, and nanoindentation. Tibial bone morphology and curvature were assessed with micro computed tomography (μCT). Bone composition was measured with Fourier transform infrared (FTIR) imaging. Vascular and osteocyte lacunar porosity were assessed by synchrotron computed tomography. Fbn1C1041G/+ mice exhibited long bone overgrowth and osteopenia consistent with the MFS phenotype. Trabecular thickness was lower in Fbn1C1041G/+ mice but cortical bone microarchitecture was similar in Fbn1C1041G/+ and LC mice. Whole bone curvature was straighter below the tibio-fibular junction in the medial–lateral direction and more curved above in LC compared to Fbn1C1041G/+ mice. The bone matrix crystallinity was 4 % lower in Fbn1C1041G/+ mice compared to LC, implying that mineral platelets in LCs have greater crystal size and perfection than Fbn1C1041G/+ mice. Structural and mechanical properties were similar between genotypes. Cortical diaphyseal lacunar porosity was lower in Fbn1C1041G/+ mice compared to LC; this was a result of the average volume of an individual osteocyte lacunae being smaller. These data provide valuable insights into the bone phenotype and its contribution to fracture risk in this commonly used mouse model of MFS.
000136291 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/RYC-2015-171562
000136291 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000136291 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000136291 700__ $$aDeVet, Taylor
000136291 700__ $$0(orcid)0000-0002-8503-9291$$aCilla, Myriam$$uUniversidad de Zaragoza
000136291 700__ $$aAlbiol, Laia
000136291 700__ $$aKavaseri, Kyle
000136291 700__ $$aAndrea, Christine
000136291 700__ $$aJulien, Catherine
000136291 700__ $$aTiedemann, Kerstin
000136291 700__ $$aPanahifar, Arash
000136291 700__ $$aAlidokht, Sima A.
000136291 700__ $$aChromik, Richard
000136291 700__ $$aKomarova, Svetlana V.
000136291 700__ $$aReinhardt, Dieter P.
000136291 700__ $$aZaslansky, Paul
000136291 700__ $$aWillie, Bettina M.
000136291 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000136291 773__ $$g23 (2024), 100155 [12 pp.]$$pMatrix biol. plus$$tMatrix biology plus$$x2590-0285
000136291 8564_ $$s6000641$$uhttps://zaguan.unizar.es/record/136291/files/texto_completo.pdf$$yVersión publicada
000136291 8564_ $$s2374595$$uhttps://zaguan.unizar.es/record/136291/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000136291 909CO $$ooai:zaguan.unizar.es:136291$$particulos$$pdriver
000136291 951__ $$a2024-07-31-09:22:19
000136291 980__ $$aARTICLE