胶原蛋白酶-3（基质金属蛋白酶-13）对软骨聚集蛋白聚糖的降解作用。

Degradation of cartilage aggrecan by collagenase-3 (MMP-13).

作者信息

Fosang A J, Last K, Knäuper V, Murphy G, Neame P J

机构信息

Orthopaedic Molecular Biology Research Unit, Melbourne University Department of Paediatrics, Royal Children's Hospital, Parkville, Australia.

出版信息

FEBS Lett. 1996 Feb 12;380(1-2):17-20. doi: 10.1016/0014-5793(95)01539-6.

DOI:10.1016/0014-5793(95)01539-6

PMID:8603731

Abstract

Degradation of the large cartilage proteoglycan aggrecan in arthritis involves an unidentified enzyme aggrecanase, and at least one of the matrix metalloproteinases. Proteinase-sensitive cleavage sites in the aggrecan interglobular domain (IGD) have been identified for many of the humman MMPs, as well as for aggrecanase and other proteinases. The major MMP expressed by chondrocytes stimulated with retinoic acid to degrade their matrix is collagenase-3 or MMP-13. Because of its potential role in aggrecan degradation we examined the specificity of MMP-13 for an aggrecan substrate. The results show that MMP-13 cleaves aggrecan in the IGD at the same site (..PEN314-FFG..) identified for other members of the MMP family, and also at a novel site ..VKP384-VFE.. not previously observed for other proteinases.

摘要

关节炎中大型软骨蛋白聚糖聚集蛋白聚糖的降解涉及一种尚未确定的酶——聚集蛋白聚糖酶，以及至少一种基质金属蛋白酶。已确定许多人类基质金属蛋白酶、聚集蛋白聚糖酶和其他蛋白酶在聚集蛋白聚糖球间结构域（IGD）中的蛋白酶敏感切割位点。用视黄酸刺激软骨细胞以降解其基质时，软骨细胞表达的主要基质金属蛋白酶是胶原酶-3或基质金属蛋白酶-13。由于其在聚集蛋白聚糖降解中的潜在作用，我们研究了基质金属蛋白酶-13对聚集蛋白聚糖底物的特异性。结果表明，基质金属蛋白酶-13在IGD中切割聚集蛋白聚糖的位点（..PEN314-FFG..）与基质金属蛋白酶家族其他成员所确定的位点相同，并且还在一个新位点..VKP384-VFE..切割，该位点以前未被其他蛋白酶观察到。