Hospital for Special Surgery, Cornell University-Weill Medical College, New York, NY 10021, USA.
Bone. 2012 Nov;51(5):920-8. doi: 10.1016/j.bone.2012.08.110. Epub 2012 Aug 15.
Understanding how the material properties of bone tissue from the various forms of osteogenesis imperfecta (OI) differ will allow us to tailor treatment regimens for affected patients. To this end, we characterized the bone structure and material properties of two mouse models of OI, the osteogenesis imperfecta mouse (oim/oim) and fragilitas ossium (fro/fro), in which bone fragility is due to a genetic defect in collagen type I and a defect in osteoblast matrix mineralization, respectively. Bones from 3 to 6 month old animals were examined using Fourier transform infrared spectroscopic imaging (FTIRI), microcomputed tomography (micro-CT), histology, and biochemical analysis. The attributes of oim/oim bone tissue were relatively constant over time when compared to wild type animals. The mineral density in oim/oim cortices and trabecular bone was higher than wild type while the bones had thinner cortices and fewer trabeculae that were thinner and more widely spaced. The fro/fro animals exhibited osteopenic attributes at 3 months. However, by 6 months, their spectroscopic and geometric properties were similar to wild type animals. Despite the lack of a specific collagen defect in fro/fro mice, both fro/fro and oim/oim genotypes exhibited abnormal collagen crosslinking as determined by FTIRI at both time points. These results demonstrate that abnormal extracellular matrix assembly plays a role in the bone fragility in both of these models.
了解不同形式成骨不全症(OI)的骨组织的材料特性如何不同,将使我们能够为受影响的患者定制治疗方案。为此,我们对两种 OI 小鼠模型——成骨不全症小鼠(oim/oim)和脆性骨(fro/fro)的骨结构和材料特性进行了表征,这两种模型中的骨脆弱性分别是由于 I 型胶原的遗传缺陷和成骨细胞基质矿化缺陷引起的。使用傅里叶变换红外光谱成像(FTIRI)、微计算机断层扫描(micro-CT)、组织学和生化分析检查了 3 至 6 个月大的动物的骨骼。与野生型动物相比,oim/oim 骨组织的属性随时间变化相对稳定。oim/oim 皮质骨和小梁骨的矿物质密度高于野生型,而骨皮质较薄,小梁较少且较薄,间距较大。fro/fro 动物在 3 个月时表现出骨质疏松的特征。然而,到 6 个月时,它们的光谱和几何特性与野生型动物相似。尽管 fro/fro 小鼠中没有特定的胶原缺陷,但在这两个时间点,FTIRI 均表明 fro/fro 和 oim/oim 基因型的胶原交联异常。这些结果表明,异常的细胞外基质组装在这两种模型的骨脆弱性中都发挥了作用。