Severely Impaired Bone Material Quality in Chihuahua Zebrafish Resembles Classical Dominant Human Osteogenesis Imperfecta
Severely Impaired Bone Material Quality in Chihuahua Zebrafish Resembles Classical Dominant Human Osteogenesis Imperfecta
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DOI：
10.1002/jbmr.3445
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发表时间：
2018-08-01
影响因子：
6.2
通讯作者：
Busse, Bjoern
中科院分区：
文献类型：
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作者：
Fiedler, Imke A. K.;Schmidt, Felix N.;Busse, Bjoern
绝大多数成骨不全（OI）患者的过度骨骼变形和脆性骨折是骨质量大幅下降的结果。由于骨的力学性能取决于小尺度的组织特征，因此评估骨成骨不全在骨的微观和纳米尺度上的表现是至关重要的。在这种背景下，吉娃娃（Chi/+）斑马鱼在I型胶原蛋白α - 1链中携带杂合甘氨酸取代，最近被提出作为经典显性成骨不全的合适动物模型，表现出骨骼畸形，矿化模式改变，体型较小。本研究通过显微计算机断层扫描（micro-CT）、组织形态学测量、定量背散射电子成像、傅里叶变换红外光谱、纳米压痕和x射线显微镜，在多个长度尺度上评估Chi/+的骨质量特性。在骨骼水平，Chi/+表现出较小的体型、畸形和肋骨骨折痂。全骨水平形态学变化表明Chi/+椎体尺寸较小，厚度较小，形状扭曲。在组织水平上，与野生型斑马鱼相比，Chi/+表现出更高的矿化程度、更低的胶原成熟度、更低的矿物质成熟度、改变的成骨细胞形态和更低的骨细胞腔隙密度。Chi/+骨的细胞、组成和结构特性的改变可以解释局部力学特性受损，从而促进Chi/+骨整体脆性的增加。因此，Chi/+骨质量的定量评估进一步验证了该突变体作为反映人类经典显性成骨不全相关骨特征的重要模型。(c) 2018年美国骨与矿物研究学会。
Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Because the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how OI manifests at the micro-and nanoscale of bone. In this context, the Chihuahua (Chi/+) zebrafish, carrying a heterozygous glycine substitution in the alpha 1 chain of collagen type I, has recently been proposed as a suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns, and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier-transform infrared spectroscopy, nanoindentation, and X-ray microscopy. At the skeletal level, the Chi/+ displays smaller body size, deformities, and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness, and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to wild-type zebrafish. The alterations in the cellular, compositional, and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/+. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant OI. (c) 2018 American Society for Bone and Mineral Research.