期刊
JOURNAL OF BIOMECHANICS
卷 65, 期 -, 页码 145-153出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jbiomech.2017.10.018
关键词
Premature aging; Osteoporosis; Finite element analysis; Bone composition; Bone strength
资金
- German Federal Ministry of Education and Research [TP5/DIMEOs]
- German Research Foundation [WI3761/4-1, CH1123/4-1, K02891/4-1, FOR2165]
- National Institutes of Health [AR043125]
- European Community's Seventh Framework Programme [SYBIL:602300]
- National Natural Science Foundation of China [11702008]
- Beijing University of Technology Seed Fund for International Collaboration [015000514117514]
- Shriners Hospitals for Children
- Roseau de recherche en sante buccodentaire et osseuse recruitment aid program
Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the COMB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPnel) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the Gorab(Prx1) 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 GorabPnel tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to litter mate 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 Gorab(Prx1) 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 Gorab(Prx1) 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. (C) 2017 Elsevier Ltd. All rights reserved.
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