RESUMO
The aim of this study was to explore the hierarchical arrangement of structural properties in cortical and trabecular bone and to determine a mathematical model that accurately predicts the tissue's mechanical properties as a function of these indices. By using a variety of analytical techniques, we were able to characterize the structural and compositional properties of cortical and trabecular bones, as well as to determine the suitable mathematical model to predict the tissue's mechanical properties using a continuum micromechanics approach. Our hierarchical analysis demonstrated that the differences between cortical and trabecular bone reside mainly at the micro- and ultrastructural levels. By gaining a better appreciation of the similarities and differences between the two bone types, we would be able to provide a better assessment and understanding of their individual roles, as well as their contribution to bone health overall.
Assuntos
Densidade Óssea/fisiologia , Fêmur/fisiologia , Fêmur/ultraestrutura , Modelos Biológicos , Animais , Força Compressiva/fisiologia , Simulação por Computador , Módulo de Elasticidade/fisiologia , Feminino , Dureza/fisiologia , Modelos Anatômicos , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Resistência à Tração/fisiologiaRESUMO
Three-point bending technology has been widely used in the measurement of bone strength. Quantitative trait loci (QTLs) for bone strength have been identified using mouse femurs. In this study, we investigate the use of mouse tibiae in identification of QTLs that regulate bone strength. Mouse tibiae were from a F(2) population derived from C57BL/6J (B6) and C3H/HeJ (C3H). Three-point bending was measured using ISO 4049, with the support width adjustable to accommodate specimen sizes outside the scope of ISO 4049. The strain rate is selectable from 0.05 to 500 mm per min. All stress strain diagrams are recorded and retrieved in digital electronic form. Genome scan was performed in The Jackson Laboratory (TJL). QTL mapping was conducted using Map Manager QTX software. Data show that (i) both elastic modulus (stiffness) and maximum loading (strength) value appear as normal distributions, suggesting that multiple genetic factors control the bone strength; (ii) 11 QTLs, accounting for 90% of variation for strength, have been detected. More than half QTLs of three-point bending are located on the same locations of bone density earlier identified from mouse femurs; (iii) a major QTL of femoral and vertebral bone mineral density (BMD) was not detected for bone strength of tibiae; (iv) the QTL on chromosome 4 has extremely high LOD score of 31.8 and represents 60% of the variation of bone strength; and (v) four QTLs of stiffness (chromosomes 2, 11, 15 and 19) have been identified.
Assuntos
Densidade Óssea/genética , Camundongos Endogâmicos C3H/genética , Camundongos Endogâmicos C57BL/genética , Locos de Características Quantitativas/genética , Tíbia/fisiologia , Animais , Cromossomos de Mamíferos/genética , Cruzamentos Genéticos , Módulo de Elasticidade/fisiologia , Feminino , Genótipo , Masculino , Camundongos , Suporte de Carga/fisiologiaRESUMO
Use of nanoindentation technology to identify quantitative trait loci (QTL) that regulate bone properties represents a novel approach to improving our understanding of molecular mechanisms that control bone matrix properties. Tibiae for QTL mapping were from an F2 population derived from C57BL/6J and C3H/HeJ. A nanoindenter (Triboindenter; Hysitron, Minneapolis, MN) was used to conduct indentation tests on transverse sections. Genotyping was performed in The Jackson Laboratory. QTL mapping was conducted using software. We found that (1) tibiae from mice at 16 weeks of age were mature and suitable for measurement by a nanoindentor; (2) both stiffness modulus and hardness modulus in the F2 population appeared to have normal distributions, which suggested that multiple genetic factors control the bone properties; and (3) QTL for hardness were identified from five chromosomes (Chr 8, 12, 13, 17, and 19) and for stiffness, from four chromosomes (Chr 3, 8, 12, and 13). Among all detected QTL, one at the same location on Chr 12 was detected for both hardness and stiffness data. It explained the highest percentage of phenotypic variation in bone properties. Using nanoindentation technology to identify QTL that regulate bone properties yielded as many as six different chromosomal regions. Although the actual genes remain to be identified, nanoindentation will contribute to our understanding of molecular mechanisms and normal development processes that control the matrix properties of bone.
