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Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae : a mouse model of premature aging
Publikationstyp
Journal Article
Date Issued
2017-12-08
Sprache
English
Author(s)
Yang, Haisheng
Albiol, Laia
Chan, Wing Lee
Seliger, Anne
Thelen, Michael
Thiele, Tobias
Spevak, Lyudmila
Kornak, Uwe
Journal
Volume
65
Start Page
145
End Page
153
Citation
Journal of Biomechanics 65: 145-153 (2017)
Publisher DOI
Scopus ID
Publisher
Elsevier
Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPrx1) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (p <.05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ∼two times higher tissue-level strains within the GorabPrx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that GorabPrx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the GorabPrx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO.
Subjects
Bone composition
Bone strength
Finite element analysis
Osteoporosis
Premature aging
DDC Class
610: Medicine, Health