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基质金属蛋白酶(MMP)-3 基因在大鼠尾加压加载诱导的椎间盘退变模型中的上调。

Matrix metalloproteinase (MMP)-3 gene up-regulation in a rat tail compression loading-induced disc degeneration model.

机构信息

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

出版信息

J Orthop Res. 2010 Aug;28(8):1026-32. doi: 10.1002/jor.21116.

DOI:10.1002/jor.21116
PMID:20162718
Abstract

The rodent static compression loading-induced disc degeneration model still has important gaps among the radiographic, magnetic resonance imaging (MRI), and histological schemes and the acute and chronic expression of catabolic genes such as matrix metalloproteinase (MMP)-3. Our objectives were to assess the validity of a rat tail two-disc static compression model and to elucidate a representative catabolic marker, MMP-3 gene alterations, throughout the degenerative process. Static compression at 1.3 MPa for up to 56 days produced progressive disc height loss in radiographs, lower nucleus intensity on T2-weighted MRIs, and histomorphological degeneration. Real-time RT-PCR mRNA quantification showed significant MMP-3 up-regulation in nucleus pulposus cells from 7 days and a significantly progressive increase as the loading duration lengthened, with high correlations to radiological degenerative scores. Immunohistochemistry demonstrated progressively increased positive staining for MMP-3. These results validate this animal model for disc degeneration research. Progressive mRNA and protein-distributional up-regulations indicate the significant role of MMP-3 and its feasibility as a disc degenerative marker. This model should prove useful for investigating the pathomechanism and for evaluating molecular therapies for degenerative disc disease.

摘要

鼠尾两节静态压迫致椎间盘退变模型在放射学、磁共振成像(MRI)和组织学方案以及基质金属蛋白酶(MMP)-3 等分解代谢基因的急性和慢性表达方面仍存在重要差距。我们的目的是评估大鼠尾两节静态压缩模型的有效性,并阐明一个有代表性的分解代谢标志物 MMP-3 基因的改变,贯穿整个退行性过程。1.3 MPa 的静态压迫持续 56 天可导致放射学上椎间盘高度逐渐丧失、T2 加权 MRI 上核强度降低以及组织形态学退变。实时 RT-PCR mRNA 定量显示,从第 7 天起,核内细胞的 MMP-3 表达显著上调,并随着加载时间的延长而显著逐渐增加,与放射学退行性评分高度相关。免疫组织化学显示 MMP-3 的阳性染色逐渐增加。这些结果验证了该动物模型在椎间盘退变研究中的有效性。mRNA 和蛋白质分布的逐渐上调表明 MMP-3 的重要作用及其作为椎间盘退变标志物的可行性。该模型应有助于研究发病机制,并评估退行性椎间盘疾病的分子治疗。

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