Roles of metalloproteinase-3 and aggrecanase 1 and 2 in aggrecan cleavage during human meniscus degeneration.

Roles of metalloproteinase-3 and aggrecanase 1 and 2 in aggrecan cleavage during human meniscus degeneration.
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DOI:
10.4081/or.2009.e14
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发表时间:
2009-10-10
期刊:
影响因子:
2.1
通讯作者:
Ishiguro N
Ishiguro N
中科院分区:
其他
文献类型:
--
作者:
Ishihara G;Kojima T;Saito Y;Ishiguro N

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半月板对膝关节的正常功能起着重要作用。最近有报道半月板退变与骨关节炎(OA)的进展有关。然而,在骨性关节炎过程中,降解酶对半月板基质的影响,主要是I型胶原和聚集素,我们知之甚少。本研究探讨了金属蛋白酶(MMPs)和阿胶聚糖酶(Aggrecanase)对人半月板聚集素破坏的影响。在半月板部分切除术中收集了18个修剪的半月板部分。根据胶原束的损伤程度,将标本按改良的Copenhaver分类分为3组。进行组织学和免疫组织化学研究。切片用抗基质金属蛋白酶-3、聚集性聚糖酶1和2的抗体及其聚集素的特异性切割位点进行染色。分别测定其在半月板内、浅、外深部的定位和染色比例。随着半月板的退变,软骨细胞样细胞数量增多。基质金属蛋白酶-3和聚集聚糖酶1和2主要在软骨细胞样细胞中表达和激活。基质金属蛋白酶-3的表达和活化随着软骨细胞样细胞的退变和增多而增加。Aggrecanase 1的表达随退变的变化不明显,而Aggrecanase 2的表达与退变的进展有关。在软骨细胞样细胞中表达的基质金属蛋白酶-3和聚集聚糖酶,尤其是聚集聚糖酶2,可能在人半月板聚集聚糖降解过程中发挥重要作用。
The meniscus plays important roles in proper knee function. It was recently reported that meniscus degeneration was associated with progression of osteoarthritis (OA). However, little is known about the effects of degradative enzymes on the meniscus matrix, primarily collagen type I and aggrecan, during OA. This study examined the effects of metalloproteinase (MMP) and aggrecanase on the destruction of aggrecan in the human meniscus. Eighteen trimmed meniscus portions were collected during partial menisectomy. Specimens were categorized into 3 groups according to the modified Copenhaver classification based on the degrees of damage to collagen bundles. Histological and immunohistochemical studies were conducted. Sections were stained with antibodies against MMP-3, aggrecanase 1 and 2, and their specific cleavage sites of aggrecan. Their localizations and staining ratios in the inner superficial and outer deep zones of the meniscus were determined separately. The population of chondrocyte-like cells increased with degeneration of the meniscus. MMP-3 and aggrecanase 1 and 2 are primarily expressed and activated in chondrocyte-like cells. MMP-3 expression and activation increased with degeneration and the population of chondrocyte-like cells. Changes in aggrecanase 1 expression with the degeneration were not clearly detected, whereas the expression of aggrecanase 2 was associated with progression of degeneration. MMP-3 and aggrecanases, particularly aggrecanase 2, expressed in chondrocyte-like cells could play important roles in aggrecan degradation in the human meniscus.