Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model.

Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model.
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DOI:
10.1097/phm.0000000000000818
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发表时间:
2018-03
影响因子:
3
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学3区
文献类型:
--
作者:
Tian Z;Ma X;Yasen M;Mauck RL;Qin L;Shofer FS;Smith LJ;Pacifici M;Enomoto-Iwamoto M;Zhang Y

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椎间盘(IVD)随着年龄的增长和损伤后逐渐退行性变。在这项研究中,我们旨在通过小鼠尾巴IVD损伤模型来描述椎间盘退变的早期分子事件。我们建立了一种在透视引导下经皮微创诱导小鼠尾部IVD损伤的方法。将损伤ivd的形态学和分子变化与相邻完整水平的基线特征进行比较。针刺后,尾ivd表现出随时间变化的组织学变化。损伤后2天至4周,聚集蛋白新表位VDIPEN明显。崩解素和金属蛋白酶结构域蛋白8 (adam8)是一种表面蛋白酶,已知在IVD中切割纤维连接蛋白。adam8基因表达在损伤后各时间点均升高,而C-X-C基序趋化因子配体(cxcl)-1基因表达在损伤后2 d和2周均有统计学意义。损伤后第2天,ⅰ型胶原基因表达开始下降,2周后,ⅰ型胶原基因表达升高,ⅱ型胶原基因表达无明显变化。细胞外基质基因表达模式与损伤后纤维软骨形成一致。小鼠尾部ivd在针刺后发生变性,表现为组织学改变和聚集蛋白降解。该微创尾IVD损伤模型对研究IVD退行性变及修复机制有一定的指导意义。
Intervertebral disc (IVD) degenerates progressively with age and following injuries. In this study, we aimed to characterize early molecular events underlying disc degeneration using a mouse tail IVD injury model. We have established a transcutaneous minimally invasive approach to induce mouse tail IVD injury under fluoroscopic guidance. Morphological and molecular changes in the injured IVDs are compared with the baseline features of adjacent intact levels. Following needle puncture, tail IVDs exhibited time-dependent histological changes. The aggrecan neoepitope VDIPEN is evident from 2 days to 4 weeks post injury. A disintegrin and metalloproteinase domain-containing protein 8 (adam8) is a surface protease known to cleave fibronectin in the IVD. Gene expression of adam8 was elevated at all time points post injury, while the increase of C-X-C motif chemokine ligand (cxcl)-1 gene expression is statistically significant at 2 days and 2 weeks post injury. Type I collagen gene expression decreased initially at day 2, but increased at 2 weeks post injury, while no significant change in type II collagen gene expression was observed. The extracellular matrix gene expression pattern is consistent with fibrocartilage formation post injury. Mouse tail IVDs degenerate post needle puncture, as demonstrated by histological changes and aggrecan degradation. The minimally invasive tail IVD injury model should prove useful to investigators studying mechanisms of IVD degeneration and repair.