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The assembly and degradation of extracellular matrix (ECM) molecules are crucial processes during bone development. In this study, we show that ECM remodeling is a critical rate-limiting step in endochondral bone formation. Matrix metalloproteinase (MMP) 13 (collagenase 3) is poised to play a crucial role in bone formation and remodeling because of its(More)
An enzyme-linked absorbent assay for the determination of hyaluronan (HA) has been developed. The procedure is sensitive, simple and is based on a microtitre plate format. The assay involves competition between HA absorbed to the plate and HA free in solution for binding to biotinylated cartilage proteoglycan binding region (G1 domain). The range of the(More)
OBJECTIVE To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA). METHODS OA was surgically induced in the knees of MMP-13-knockout mice and wild-type mice, and mice were compared. Histologic scoring of femoral and tibial cartilage aggrecan loss (0-3 scale), erosion (0-7 scale), and chondrocyte hypertrophy(More)
In the mouse, proteolysis in the aggrecan interglobular domain is driven by ADAMTS-5, and mice deficient in ADAMTS-5 catalytic activity are protected against aggrecan loss and cartilage damage in experimental models of arthritis. Here we show that despite ablation of ADAMTS-5 activity, aggrecanolysis can still occur at two preferred sites in the chondroitin(More)
The recent discovery of ADAMTS-5 as the major aggrecanase in mouse cartilage came as a surprise. A great deal of research had focused on ADAMTS-4 and much less was known about the regulation, expression and activity of ADAMTS-5. Two years on, it is still not clear whether ADAMTS-4 or ADAMTS-5 is the major aggrecanase in human cartilage. On the one hand(More)
OBJECTIVE To develop proteomics to analyze mouse cartilage degradation and correlate transcriptional and translational responses to catabolic stimuli. METHODS Proteomic techniques were used to analyze catabolism in mouse femoral head cartilage. Using specific methods to prepare cartilage extracts and conditioned media for 2-dimensional polyacrylamide gel(More)
Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is found widely expressed in body tissues, including the(More)
We have used progressive chondroitinase digestion of pig aggrecan in conjunction with ELISA assays and disaccharide analysis to derive information about the pattern of 4- and 6-sulphation in chondroitin sulphate chains. Digestion with chondroitinase ABC resulted in the release of mainly disaccharides from the nonreducing terminal of chondroitin sulphate(More)
In healthy cartilage, effective weight-bearing requires a high concentration of intact aggrecan. Degradation and loss of aggrecan are features of osteoarthritis (OA). It is unclear whether ADAMTS-4, ADAMTS-5, or both of these aggrecanases from the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzyme family, are responsible for(More)
We have developed a monoclonal antibody AF-28 that specifically recognizes a neo-epitope on polypeptides with N-terminal FFGVG ... sequences. This sequence is found at the N-terminus of aggrecan fragments that have been digested with matrix metalloproteinases (MMPs). By immunoblotting, monoclonal antibody AF-28 specifically detected G2 fragments derived(More)