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Journal ArticleDOI

Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.

TLDR
The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.
Abstract
We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.

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Citations
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Journal ArticleDOI

How Matrix Metalloproteinases Regulate Cell Behavior

TL;DR: Recent advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled.
Journal ArticleDOI

Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis

TL;DR: It is demonstrated that ADAMTS5 is the primary ‘aggrecanase’ responsible for aggrecan degradation in a murine model of osteoarthritis, and rational strategies for therapeutic intervention in osteOarthritis are suggested.
Journal ArticleDOI

Matrix metalloproteinases: role in arthritis.

TL;DR: Increasing knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.
Journal ArticleDOI

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

TL;DR: This review focuses on the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.
References
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Journal ArticleDOI

The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family.

TL;DR: Observations support the view that the cysteine-switch mechanism is applicable to all members of this gene family and offers the opportunity for multiple modes of physiological activation of these important enzymes.
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The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression.

TL;DR: An effort to share resources such that the maximum amount of gene-related data is obtained with the last redundancy is described, to have the data derived from the use of common reagents placed in public databases, and to create master arrays containing a representative cDNA clone from each gene.
Journal ArticleDOI

Prediction of the Coding Sequences of Unidentified Human Genes. X. The Complete Sequences of 100 New cDNA Clones from Brain Which Can Code for Large Proteins in vitro

TL;DR: The entire sequences of 100 cDNA clones which were screened on the basis of the potentiality of coding for large proteins in vitro were determined and the expression profiles in a variety of tissues and chromosomal locations of the sequenced clones have been determined.
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Mammalian subtilisins: The long-sought dibasic processing endoproteases

TL;DR: After many years of searching for the enzymes responsible for cleavage of mammalian proproteins and prohormones at sites comprised of pairs of basic amino acid residues (“dibasic sites”), the solution to this enigma of cell biology appears to be in sight.
Journal ArticleDOI

Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene.

TL;DR: The TSP homologous domain containing the TSP type I motif of ADAMTS-1 is functional for binding to heparin, suggesting that ADAM-TS- 1 may be a gene whose expression is associated with various inflammatory processes as well as development of cancer cachexia.
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