A Rat Tail Temporary Static Compression Model Reproduces Different Stages of Intervertebral Disc Degeneration with Decreased Notochordal Cell Phenotype
A Rat Tail Temporary Static Compression Model Reproduces Different Stages of Intervertebral Disc Degeneration with Decreased Notochordal Cell Phenotype
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DOI：
10.1002/jor.22533
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发表时间：
2014-03-01
影响因子：
2.8
通讯作者：
Nishida, Kotaro
中科院分区：
文献类型：
--
作者：
Hirata, Hiroaki;Yurube, Takashi;Nishida, Kotaro
椎间盘髓核（NP）有两种不同的细胞类型：脊索细胞（NC）和非脊索软骨细胞样细胞。在人类椎间盘中，NC在青春期丢失，这也是椎间盘开始显示退行性体征的时候。然而，很少有证据表明NC消失和椎间盘退变的发病机制之间存在联系。为了阐明这一点，设计了在1.3MPa下静态压缩0、1或7天诱导的大鼠尾椎间盘退变模型，并在术后56天进行了评估。影像学、MRI和组织形态学检查显示，压迫期间椎间盘出现退行性改变。免疫荧光显示，DAPI阳性NP细胞的数量随着压缩而减少;特别是，在较大的空泡化细胞角蛋白-8和半乳糖凝集素-3共阳性细胞（鉴定为NC）中，这种减少是显著的。TUNEL阳性细胞的比例（主要包括非NC）随着压缩而增加。定量PCR结果显示，ADAMTS-5和MMP-3的mRNA表达分别在第1天和第7天负荷组中上调。两组中聚集蛋白聚糖-1和2-1型胶原mRNA水平均下调。这种大鼠尾部暂时静态压缩模型表现出NC表型降低、凋亡细胞死亡增加以及分解代谢和合成代谢基因表达不平衡，再现了椎间盘退变的不同阶段。(c)2013年骨科研究学会。由威利期刊公司出版J Orthop Res 32：455-463，2014.
The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell typesnotochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:455-463, 2014.