All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes
All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes
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DOI：
10.1016/j.bbrc.2009.06.052
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发表时间：
2009-08-21
影响因子：
3.1
通讯作者：
Takigawa, Masaharu
中科院分区：
文献类型：
--
作者：
Hikichi, Yuichi;Yoshimura, Koji;Takigawa, Masaharu
为了阐明骨关节炎（OA）中软骨降解的机制，我们建立了一种细胞检测系统。在全反式维甲酸（ATRA）刺激下，人软骨肉瘤细胞系HCS-2/8增加了失活牛鼻软骨（BNC）蛋白多糖的释放，结果表明膜结合金属蛋白酶（s）参与了蛋白多糖的释放。因此，我们集中在诱导的解整合素和金属蛋白酶（ADAM）超家族ATRA刺激。在所有测试亚当斯中，只有ADAM 2/8在HCS-2/8细胞和人原代软骨细胞中被ATRA诱导。我们发现，转染的ADAM 28或其可变剪接可溶形式增强蛋白聚糖释放的细胞测定，然而，突变的可溶形式，其中一部分的去整合素结构域被删除没有蛋白聚糖释放活性，这意味着该域的重要性，为酶的本地化和基板识别软骨降解骨关节炎。(C)2009 Elsevier Inc. All rights reserved.
In order to elucidate the mechanism of cartilage degradation in osteoarthritis (OA), we established a cell assay system. Under the stimulation of all-trans retinoic acid (ATRA), the human chondrosarcoma, cell line HCS-2/8 increased proteoglycan release from inactivated bovine nasal cartilage (BNC) and the results suggested the involvement of membrane-bound metalloproteinase(s). Therefore, we focused on the induction of a disintegrin and metalloproteinase (ADAM) superfamily upon ATRA stimulation. Of all ADAMs tested, only ADAM28 was induced by ATRA in HCS-2/8 cells and also in human primary chondrocytes. We found that transfection of ADAM28 or its alternatively spliced soluble form augmented proteoglycan release in the cell assay; however, a mutant soluble form in which a portion of the disintegrin domain was deleted did not have proteoglycan-releasing activity, implying the importance of the domain for enzyme localization and substrate recognition for cartilage degradation in OA. (C) 2009 Elsevier Inc. All rights reserved.