Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
Department of Bioengineering, Clemson University, Clemson, SC.
J Struct Biol. 2021 Jun;213(2):107708. doi: 10.1016/j.jsb.2021.107708. Epub 2021 Feb 11.
Osteogenesis imperfecta (OI or brittle bone disease) is a group of genetic disorders of the connective tissues caused mainly by mutations in the genes encoding collagen type I. Clinical manifestations of OI include skeletal fragility, bone deformities, and severe functional disabilities, such as hearing loss. Progressive hearing loss, usually beginning in childhood, affects approximately 70% of people with OI with more than half of the cases involving the inner ear. There is no cure for OI nor a treatment to ameliorate its corresponding hearing loss, and very little is known about the properties of OI ears. In this study, we investigate the morphology of the otic capsule and the cochlea in the inner ear of the oim mouse model of OI. High-resolution 3D images of 8-week old oim and WT inner ears were acquired using synchrotron microtomography. Volumetric morphometric measurements were conducted for the otic capsule, its intracortical canal network and osteocyte lacunae, and for the cochlear spiral ducts. Our results show that the morphology of the cochlea is preserved in the oim ears at 8 weeks of age but the otic capsule has a greater cortical thickness and altered intracortical bone porosity, with a larger number and volume density of highly branched canals in the oim otic capsule. These results portray a state of compromised bone quality in the otic capsule of the oim mice that may contribute to their hearing loss.
成骨不全症(OI 或脆骨病)是一组主要由编码 I 型胶原的基因突变引起的结缔组织遗传疾病。OI 的临床表现包括骨骼脆弱、骨骼畸形和严重的功能障碍,如听力损失。进行性听力损失,通常始于儿童期,影响约 70%的 OI 患者,其中一半以上涉及内耳。OI 没有治愈方法,也没有治疗方法可以改善其相应的听力损失,而且对 OI 耳朵的特性知之甚少。在这项研究中,我们研究了 OI 的 oim 小鼠模型内耳中耳壳和耳蜗的形态。使用同步加速器微断层摄影术获取了 8 周大的 oim 和 WT 内耳的高分辨率 3D 图像。对耳壳、其皮质内管网络和骨细胞腔以及耳蜗螺旋管进行了体积形态计量测量。我们的结果表明,在 8 周龄时,oim 耳朵的耳蜗形态得以保留,但耳壳的皮质厚度更大,皮质内骨孔隙率发生改变,oim 耳壳中的高分支管数量和体积密度更大。这些结果描绘了 oim 小鼠耳壳中骨质量受损的状态,这可能导致他们的听力损失。