Tumor necrosis factor (TNF)-α and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) are important in osteoarthritis (OA) cartilage degradation. In the present study, we explored the interaction between the two proteins by examining the effect of TNF-α on ADAMTS-4 expression and activity in osteoarthritic chondrocytes. Human osteoarthritic chondrocytes were treated with...

Human umbilical vein endothelial cell (HUVEC)-released ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin repeats) and HUVEC-secreted von Willebrand factor (VWF) strings were investigated under static conditions that allow the accumulation and analysis of ADAMTS-13. The latter was released constitutively from HUVECs and cleaved the secreted and cell-anchored VWF strings progressiv...

BACKGROUND A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) may influence von Willebrand factor (VWF) levels and consequently the risk of myocardial infarction (MI). Moreover, ADAMTS-13 influences hemostatic plug formation in mouse models. We therefore studied their associations in the Glasgow MI Study (GLAMIS). METHODS AND RESULTS We measured ADAM...

We compared serum levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1, and MMP-3 in patients with different stages of knee osteoarthritis (OA), and investigated the clinical significance of diagnosing OA in early stages. OA patients were divided into 2 groups: early OA group (44 cases), intermediate and advanced OA grou...

The ADAMTS proteinases are a group of multidomain and secreted metalloproteinases containing the thrombospondin motifs. ADAMTS-7 is a member of ADAMTS family and plays a crucial role in the pathogenesis of arthritis. Overexpression of ADAMTS-7 gene promotes the breakdown of cartilage oligomeric matrix protein (COMP) matrix and accelerates the progression of both surgically induced osteoarthriti...

The potent aggrecanase ADAMTS-5 is constitutively secreted by chondrocytes, but it is rapidly endocytosed in normal cartilage via the cell surface endocytic receptor LRP1. Therefore it is difficult to detect the total ADAMTS-5 activity produced. In this study, we isolated a monoclonal anti-ADAMTS-5 antibody 1B7 that blocks LRP1-mediated internalization without affecting the aggrecanolytic activ...

INTRODUCTION Matrix metalloproteinases (MMPs) and 'aggrecanase' a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix (ECM) type II collagen and aggrecan, and are thus potential targets for development of OA therapies. OBJECTIVE This paper aims to provide a comprehensiv...

BACKGROUND/AIMS We investigated the unknown molecular mechanisms of Interleukin-1 (IL-1β)-induced cartilage aggrecan degeneration by aggrecanase (ADAMTS-A Disintegrin And Metalloproteinase with ThromboSpondin motifs) in human articular chondrocytes, a model mimicking human arthritis. METHODS Chondrocytes were pretreated with various pharmacological inhibitors and then stimulated with IL-1β fo...

Biosynthetic processing of fibrillar procollagens is essential for producing mature collagen monomers that polymerize into fibrils by a self-assembly process. The metalloproteinase ADAMTS-2 is the major enzyme that processes the N-propeptide of type I procollagen in the skin and also of type II and type III procollagens. Mutations in the ADAMTS-2 gene cause dermatospraxis in animals and Ehlers-...

OBJECTIVE The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative contribution of ADAMTS-4 and ADAMTS-5 to cartilage degradation upon catabolic stimulation; ii) To investi...