Expression and activity of ADAMTS-5 in synovium.

Expression and activity of ADAMTS-5 in synovium.
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ADAMTS-5 在滑膜中的表达和活性。

DOI:
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发表时间:
2001
期刊:
European Journal of Biochemistry
影响因子:
--
通讯作者:
D. Buttle
D. Buttle
中科院分区:
--
文献类型:
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作者:
M. Vankemmelbeke;I. Holen;A. Wilson;M. Z. Ilic;C. Handley;G. Kelner;M. Clark;Changlu Liu;R. Maki;David Burnett;D. Buttle

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ADAMTS蛋白酶属于金属蛋白酶的adamalysin亚家族,与多种细胞事件如形态发生、细胞迁移、血管生成、排卵和细胞外基质分解有关。聚集蛋白聚糖酶-1(ADAMTS-4)和聚集蛋白聚糖酶-2(ADAMTS-5)已在软骨中被鉴定,并且主要负责软骨聚集蛋白聚糖的分解。我们以前已经表明,滑膜,膜内衬diarthodial关节,产生可溶性聚集蛋白聚糖酶活性。我们在这里报告ADAMTS-5从人类关节炎和牛滑膜的表达,定位和活性。ADAMTS-5在滑膜中组成型表达,很少或没有重组人白细胞介素-1 α或全反式维甲酸的转录调节,这些因子先前显示上调软骨中的聚集蛋白聚糖酶活性。滑膜在体外产生的聚集蛋白聚糖酶活性和重组ADAMTS-5广泛切割聚集蛋白聚糖,导致聚集蛋白聚糖片段类似于软骨细胞衍生的聚集蛋白聚糖酶产生的片段,并且该活性被肝素抑制。ADAMTS-5在人关节炎滑膜中免疫定位,其中染色主要是细胞周围的,特别是在滑膜衬里和血管周围;还观察到一些基质染色。滑膜衍生的ADAMTS-5可能在软骨聚集蛋白聚糖分解中发挥作用的可能性进行了讨论。
ADAMTS proteinases, belonging to the adamalysin subfamily of metalloproteinases, have been implicated in a variety of cellular events such as morphogenesis, cell migration, angiogenesis, ovulation and extracellular matrix breakdown. Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) have been identified in cartilage and are largely responsible for cartilage aggrecan breakdown. We have shown previously that synovium, the membrane lining diarthrodial joints, generates soluble aggrecanase activity. We report here the expression, localization and activity of ADAMTS-5 from human arthritic and bovine synovium. ADAMTS-5 was expressed constitutively in synovium with little or no transcriptional regulation by recombinant human interleukin-1 alpha or all-trans-retinoate, factors previously shown to upregulate aggrecanase activity in cartilage. Aggrecanase activity generated by synovium in vitro and recombinant ADAMTS-5 cleaved aggrecan extensively, resulting in aggrecan fragments similar to those generated by chondrocyte-derived aggrecanases, and the activity was inhibited by heparin. ADAMTS-5 was immunolocalized in human arthritic synovium, where staining was mostly pericellular, particularly in the synovial lining and around blood vessels; some matrix staining was also seen. The possibility that synovium-derived ADAMTS-5 may play a role in cartilage aggrecan breakdown is discussed.
使用包埋在聚丙烯酰胺颗粒中的软骨蛋白聚糖底物对蛋白酶和多糖酶进行改进的测定。
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DOI: --
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