Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta
Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta
复制标题
DOI：
10.3109/03008207.2014.923860
复制
发表时间：
2014-08-01
影响因子：
2.9
通讯作者：
Wallace, Joseph M.
中科院分区：
文献类型：
--
作者：
Bart, Zachary R.;Hammond, Max A.;Wallace, Joseph M.
骨生成障碍是一种先天性疾病，通常以脆骨为特征，由编码I型胶原蛋白的基因突变引起，I型胶原蛋白是人体产生的最丰富的蛋白质。oim模型具有天然胶原突变，将其异源三聚体结构（两个α 1和一个α 2链）转化为α 1同源三聚体。胶原蛋白的这种突变可能会影响矿物质的形成，在动物中产生脆骨表型。使用多个长度尺度的测定法评估来自雄性野生型（WT）和纯合型（oim/oim）小鼠（均为12周龄）的股骨，并进行最少的样品处理，以确保接近生理状态。原子力显微镜（AFM）证明了胶原蛋白在纳米级组织中的可检测差异，这可能部分有助于通过机械测试和参考点压痕（RPI）获得的材料和结构行为的改变。从mu-计算机断层扫描和拉曼光谱获得的几何和化学结构的变化表明骨变小，骨小梁结构减少，化学成分改变。oim/oim小鼠中组织材料特性的降低可能是由胶原纤维结构的变化驱动的，减少了可用于矿物质成核和生长的空间，这得到了矿物质结晶度降低的支持。这种性质的多尺度分析在评估分子如何改变化合物以产生降解的脆性骨表型方面提供了很多。
Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two alpha 1 and one alpha 2 chains) into alpha 1 homotrimers. This mutation in collagen may impact formation of the mineral, creating a brittle bone phenotype in animals. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained from mu-Computed Tomography and Raman spectroscopy indicate a smaller bone with reduced trabecular architecture and altered chemical composition. Decreased tissue material properties in oim/oim mice are likely driven by changes in collagen fibril structure, decreasing space available for mineral nucleation and growth, as supported by a reduction in mineral crystallinity. Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.