Spinal deformity in aged zebrafish is accompanied by degenerative changes to their vertebrae that resemble osteoarthritis.
Spinal deformity in aged zebrafish is accompanied by degenerative changes to their vertebrae that resemble osteoarthritis.
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DOI：
10.1371/journal.pone.0075787
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hammond CL
中科院分区：
文献类型：
--
作者：
Hayes AJ;Reynolds S;Nowell MA;Meakin LB;Habicher J;Ledin J;Bashford A;Caterson B;Hammond CL
与年龄相关的脊柱退行性变化是发病的一个重要原因，在全世界范围内具有相当大的社会经济影响。通过开发实验模型加深对这些变化的理解可能会导致现有临床治疗方案的改进。斑马鱼是骨骼发生研究的成熟模型，在老年学研究中具有巨大潜力。随着年龄的增长，斑马鱼的脊柱经常出现严重畸形，以前将其归因于躯干肌张力降低。在这项研究中，我们评估了 1、2 和 3 岁时斑马鱼脊柱骨和软骨的退行性变化。我们发现脊柱畸形/弯曲的频率和严重程度随着年龄的增长而增加。最严重的表型是部分或完全椎骨脱位以及关节边缘椎骨局部增厚。 MicroCT 检查显示出微小的缺陷、骨折和形态学证据，表明衰老过程中椎骨内存在骨侵蚀和重塑（即骨赘），但骨密度没有显着变化。光和电子显微镜检查揭示了细胞形态与年龄相关的显着变化，提示软骨下垂和椎体软骨的组织重塑，特别是在细胞周微环境内。通过 HPLC 对脊柱进行的糖胺聚糖分析表明，总硫酸软骨素二糖的产量与年龄相关，持续增加，但硫酸化模式没有变化，这得到了免疫组织化学分析的支持。免疫组织化学可强烈识别椎体软骨内的所有三种软骨素/硫酸皮肤素亚型（C-0-S、C-4-S/DS 和 C-6-S），特别是在细胞周微环境中。相比之下，硫酸角质素特异性地免疫定位于椎间盘的脊索组织，并且其标记随着年龄的增长而减少。总之，这些观察结果提出了这样的前景：斑马鱼除了模拟骨骼发育外，还可能在模拟衰老过程中影响骨骼的与年龄相关的退行性变化方面具有实用性。
Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking age-related changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.
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影响因子：
4.9
作者：
Erwin WM;Islam D;Inman RD;Fehlings MG;Tsui FW
通讯作者：
Tsui FW
影响因子：
3
作者：
Haga, Yutaka;Dominique, Vincent J., III;Du, Shao Jun
通讯作者：
Du, Shao Jun
影响因子：
3.7
作者：
Fiaz, Ansa W.;Leon-Kloosterziel, Karen M.;Kranenbarg, Sander
通讯作者：
Kranenbarg, Sander
影响因子：
4.8
作者：
Holmborn, Katarina;Habicher, Judith;Ledin, Johan
通讯作者：
Ledin, Johan
影响因子：
64.8
作者：
COUCHMAN, JR;CATERSON, B;BAKER, JR
通讯作者：
BAKER, JR