A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis (2008)
Martin, Dianna C., Atmuri, V., Hemming, R. J., Farley, J., Mort, J. S., Byers, Sharon, ...
Copyright © The Author 2008. Published by Oxford University Press. All rights reserved.
A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis (2008)
Martin, Dianna C., Atmuri, V., Hemming, R. J., Farley, J., Mort, J. S., Byers, Sharon, ...
Copyright © The Author 2008. Published by Oxford University Press. All rights reserved.
The use of cleavage site specific antibodies to delineate protein processing and breakdown pathways.
The hydrolysis of peptide bonds is an integral part of most physiological and pathological processes, yet knowledge is often lacking as to which peptide bonds are cleaved, in which protein...
Nguyen, Q, Mort, J S, Roughley, P J
An imbalance between extracellular proteinases and their inhibitors is thought to underlie cartilage degradation. In cultures of adult cartilage, prostromelysin mRNA levels were much higher than...
Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
Coulombe, R, Grochulski, P, Sivaraman, J, Ménard, R, Mort, J S, Cygler, M
Cathepsin L is a member of the papain superfamily of cysteine proteases and, like many other proteases, it is synthesized as an inactive proenzyme. Its prosegment shows little homology to that of...
Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B.
Nguyen, Q, Mort, J S, Roughley, P J
The degradative actions of cathepsins L and B on human articular-cartilage proteoglycan aggregates were examined. Cathepsin L was found to be much more extensive than cathepsin B in degrading...
Mach, L, Schwihla, H, Stüwe, K, Rowan, A D, Mort, J S, Glössl, J
In order to elucidate the processing mechanism of the lysosomal cysteine proteinase, cathepsin B, in mammalian cells, recombinant rat and human cathepsin B precursors were expressed in Saccharomyces...
Rowan, A D, Feng, R, Konishi, Y, Mort, J S
Electrospray mass spectrometric techniques were used to demonstrate that mature (single-chain) recombinant rat cathepsin B is capable of sequentially removing the three dipeptides which comprise the...
Non-proteoglycan forms of biglycan increase with age in human articular cartilage.
Roughley, P J, White, R J, Magny, M C, Liu, J, Pearce, R H, Mort, J S
Polyclonal anti-peptide antibodies were raised to the C-terminal regions of human biglycan and decorin. These antibodies were used in immunoblotting to study structural variations with age in the...
Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein.
Nguyen, Q, Murphy, G, Hughes, C E, Mort, J S, Roughley, P J
The actions of human recombinant stromelysins-1 and -2, collagenase, gelatinases A and B and matrilysin on neonatal human proteoglycan aggregates were examined. With the exception of gelatinase B,...
Hughes, C E, Caterson, B, Fosang, A J, Roughley, P J, Mort, J S
Monoclonal antibodies have been prepared that react specifically with the neoepitopes present on proteoglycan degradation products generated from the proteolytic cleavage of aggrecan in the...
Björk, I, Pol, E, Raub-Segall, E, Abrahamson, M, Rowan, A D, Mort, J S
The importance of the N-terminal region of human cystatin C or chicken cystatin for the kinetics of interactions of the inhibitors with four cysteine proteinases was characterized. The association...
Nguyen, Q, Murphy, G, Roughley, P J, Mort, J S
Cartilage proteoglycan aggregates were subjected to degradation by a metalloproteinase, capable of degrading proteoglycan, released from cartilage in culture. This proteinase was demonstrated to be...
Roberts, C R, Roughley, P J, Mort, J S
We have previously shown that treatment of neonatal human articular-cartilage proteoglycan aggregates with H2O2 results in loss of the ability of the proteoglycan subunits to interact with hyaluronic...
Roughley, P J, White, R J, Poole, A R, Mort, J S
High-buoyant-density proteoglycan aggregates could not be prepared from extracts of adult human cartilage by associative CsCl-density-gradient centrifugation with a starting density of 1.68 g/ml,...
Campbell, I K, Roughley, P J, Mort, J S
Interleukin 1 stimulation of human articular cartilage in organ culture produced the concomitant release of proteoglycan fragments and latent metalloproteinase. The released fragments ranged in size...
Roberts, C R, Mort, J S, Roughley, P J
The effects of treatment of purified neonatal human articular-cartilage proteoglycan aggregate with H2O2 were studied. (1) Exposure of proteoglycan aggregate to H2O2 resulted in depolymerization of...
Buttle, D J, Abrahamson, M, Burnett, D, Mort, J S, Barrett, A J, Dando, P M, ...
The high-Mr alkali-stable form of cathepsin B was purified from purulent human sputum. It was shown to solubilize proteoglycan monomer entrapped in polyacrylamide at a rate comparable with that of...
Mort, J S, Poole, A R, Roughley, P J
Link proteins were identified immunologically in human articular-cartilage protein preparations from various individuals. Irrespective of age, all cartilages contained three link proteins of mol.wts....
Mort, J S, Caterson, B, Poole, A R, Roughley, P J
Human articular-cartilage link proteins are resolved into three components by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, indicative of three different structures. The action of the...
Interrelationship of active and latent secreted human cathepsin B precursors.
Two high-Mr forms of cathepsin B have been described previously, both of which are stable at alkaline pH, in contrast with the lysosomal proteinase. One form is latent and activated by pepsin...
A cysteine proteinase secreted from human breast tumours is immunologically related to cathepsin B.
Recklies, A D, Poole, A R, Mort, J S
The stable cathepsin B-like cysteine (thiol) proteinase secreted from human breast tumours in culture was shown to be destabilized by mercurial compounds. After such treatment the enzyme cross-reacts...
Presence of pro-forms of decorin and biglycan in human articular cartilage.
Roughley, P J, White, R J, Mort, J S
The proteoglycans decorin and biglycan in extracts of human articular cartilage were analysed by SDS/PAGE and immunoblotting, using antisera raised to peptide sequences present in the pro-regions and...
Aggrecan degradation in human intervertebral disc and articular cartilage.
Sztrolovics, R, Alini, M, Roughley, P J, Mort, J S
Aggrecan degradation in human intervertebral disc and articular cartilage has been studied by using anti-neoepitope antibodies specific for the N-terminal degradation products generated by cleavage...
Mort, J S, Magny, M C, Lee, E R
Previously, only matrix metalloproteinases were believed capable of cleaving the cartilage proteoglycan, aggrecan, between Asn341 and Phe342, to yield a small G1 fragment terminating in the residues...
Sztrolovics, R, White, R J, Poole, A R, Mort, J S, Roughley, P J
A bovine nasal-cartilage culture system has been utilized to analyse the catabolic events occurring in response to interleukin-1beta over a 14-day period. An early event following the start of...
Little, C B, Flannery, C R, Hughes, C E, Mort, J S, Roughley, P J, Dent, C, ...
The importance of aggrecanase versus matrix metalloproteinase (MMP) enzymic activities in the degradation of aggrecan in normal and osteoarthritic (OA) articular cartilage in vitro was studied in...
Link protein as a monitor in situ of endogenous proteolysis in adult human articular cartilage.
Nguyen, Q, Liu, J, Roughley, P J, Mort, J S
The link protein components of proteoglycan aggregates in adult human articular cartilage show heterogeneity due to proteolysis. Cleavages near the N-terminus of the intact link proteins, before...
The use of cleavage site specific antibodies to delineate protein processing and breakdown pathways.
The hydrolysis of peptide bonds is an integral part of most physiological and pathological processes, yet knowledge is often lacking as to which peptide bonds are cleaved, in which protein...
Nguyen, Q, Mort, J S, Roughley, P J
An imbalance between extracellular proteinases and their inhibitors is thought to underlie cartilage degradation. In cultures of adult cartilage, prostromelysin mRNA levels were much higher than...
Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
Coulombe, R, Grochulski, P, Sivaraman, J, Ménard, R, Mort, J S, Cygler, M
Cathepsin L is a member of the papain superfamily of cysteine proteases and, like many other proteases, it is synthesized as an inactive proenzyme. Its prosegment shows little homology to that of...
Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B.
Nguyen, Q, Mort, J S, Roughley, P J
The degradative actions of cathepsins L and B on human articular-cartilage proteoglycan aggregates were examined. Cathepsin L was found to be much more extensive than cathepsin B in degrading...
Mach, L, Schwihla, H, Stüwe, K, Rowan, A D, Mort, J S, Glössl, J
In order to elucidate the processing mechanism of the lysosomal cysteine proteinase, cathepsin B, in mammalian cells, recombinant rat and human cathepsin B precursors were expressed in Saccharomyces...
Rowan, A D, Feng, R, Konishi, Y, Mort, J S
Electrospray mass spectrometric techniques were used to demonstrate that mature (single-chain) recombinant rat cathepsin B is capable of sequentially removing the three dipeptides which comprise the...
Non-proteoglycan forms of biglycan increase with age in human articular cartilage.
Roughley, P J, White, R J, Magny, M C, Liu, J, Pearce, R H, Mort, J S
Polyclonal anti-peptide antibodies were raised to the C-terminal regions of human biglycan and decorin. These antibodies were used in immunoblotting to study structural variations with age in the...
Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein.
Nguyen, Q, Murphy, G, Hughes, C E, Mort, J S, Roughley, P J
The actions of human recombinant stromelysins-1 and -2, collagenase, gelatinases A and B and matrilysin on neonatal human proteoglycan aggregates were examined. With the exception of gelatinase B,...
Hughes, C E, Caterson, B, Fosang, A J, Roughley, P J, Mort, J S
Monoclonal antibodies have been prepared that react specifically with the neoepitopes present on proteoglycan degradation products generated from the proteolytic cleavage of aggrecan in the...
Björk, I, Pol, E, Raub-Segall, E, Abrahamson, M, Rowan, A D, Mort, J S
The importance of the N-terminal region of human cystatin C or chicken cystatin for the kinetics of interactions of the inhibitors with four cysteine proteinases was characterized. The association...
Nguyen, Q, Murphy, G, Roughley, P J, Mort, J S
Cartilage proteoglycan aggregates were subjected to degradation by a metalloproteinase, capable of degrading proteoglycan, released from cartilage in culture. This proteinase was demonstrated to be...
Roberts, C R, Roughley, P J, Mort, J S
We have previously shown that treatment of neonatal human articular-cartilage proteoglycan aggregates with H2O2 results in loss of the ability of the proteoglycan subunits to interact with hyaluronic...
Roughley, P J, White, R J, Poole, A R, Mort, J S
High-buoyant-density proteoglycan aggregates could not be prepared from extracts of adult human cartilage by associative CsCl-density-gradient centrifugation with a starting density of 1.68 g/ml,...
Campbell, I K, Roughley, P J, Mort, J S
Interleukin 1 stimulation of human articular cartilage in organ culture produced the concomitant release of proteoglycan fragments and latent metalloproteinase. The released fragments ranged in size...
Roberts, C R, Mort, J S, Roughley, P J
The effects of treatment of purified neonatal human articular-cartilage proteoglycan aggregate with H2O2 were studied. (1) Exposure of proteoglycan aggregate to H2O2 resulted in depolymerization of...
Buttle, D J, Abrahamson, M, Burnett, D, Mort, J S, Barrett, A J, Dando, P M, ...
The high-Mr alkali-stable form of cathepsin B was purified from purulent human sputum. It was shown to solubilize proteoglycan monomer entrapped in polyacrylamide at a rate comparable with that of...
Link protein as a monitor in situ of endogenous proteolysis in adult human articular cartilage.
Nguyen, Q, Liu, J, Roughley, P J, Mort, J S
The link protein components of proteoglycan aggregates in adult human articular cartilage show heterogeneity due to proteolysis. Cleavages near the N-terminus of the intact link proteins, before...
Mort, J S, Poole, A R, Roughley, P J
Link proteins were identified immunologically in human articular-cartilage protein preparations from various individuals. Irrespective of age, all cartilages contained three link proteins of mol.wts....
Mort, J S, Caterson, B, Poole, A R, Roughley, P J
Human articular-cartilage link proteins are resolved into three components by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, indicative of three different structures. The action of the...
Interrelationship of active and latent secreted human cathepsin B precursors.
Two high-Mr forms of cathepsin B have been described previously, both of which are stable at alkaline pH, in contrast with the lysosomal proteinase. One form is latent and activated by pepsin...
A cysteine proteinase secreted from human breast tumours is immunologically related to cathepsin B.
Recklies, A D, Poole, A R, Mort, J S
The stable cathepsin B-like cysteine (thiol) proteinase secreted from human breast tumours in culture was shown to be destabilized by mercurial compounds. After such treatment the enzyme cross-reacts...
Presence of pro-forms of decorin and biglycan in human articular cartilage.
Roughley, P J, White, R J, Mort, J S
The proteoglycans decorin and biglycan in extracts of human articular cartilage were analysed by SDS/PAGE and immunoblotting, using antisera raised to peptide sequences present in the pro-regions and...
Aggrecan degradation in human intervertebral disc and articular cartilage.
Sztrolovics, R, Alini, M, Roughley, P J, Mort, J S
Aggrecan degradation in human intervertebral disc and articular cartilage has been studied by using anti-neoepitope antibodies specific for the N-terminal degradation products generated by cleavage...
Mort, J S, Magny, M C, Lee, E R
Previously, only matrix metalloproteinases were believed capable of cleaving the cartilage proteoglycan, aggrecan, between Asn341 and Phe342, to yield a small G1 fragment terminating in the residues...
Sztrolovics, R, White, R J, Poole, A R, Mort, J S, Roughley, P J
A bovine nasal-cartilage culture system has been utilized to analyse the catabolic events occurring in response to interleukin-1beta over a 14-day period. An early event following the start of...
Little, C B, Flannery, C R, Hughes, C E, Mort, J S, Roughley, P J, Dent, C, ...
The importance of aggrecanase versus matrix metalloproteinase (MMP) enzymic activities in the degradation of aggrecan in normal and osteoarthritic (OA) articular cartilage in vitro was studied in...