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Genomes and Genes | J S MortSummaryAffiliation: McGill University Country: Canada Publications
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Publications
The mechanism of aggrecan release from cartilage differs with tissue origin and the agent used to stimulate catabolismRobert Sztrolovics
Joint Diseases Laboratory, Shriners Hospital for Children, McGill University, Montreal, Quebec, Canada H3G 1A6
Biochem J 362:465-72. 2002....- Histone deacetylases--a new target for suppression of cartilage degradation?John S Mort
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, Quebec, Canada
Arthritis Res Ther 7:155-6. 2005..This family of enzymes is therefore a promising target for therapeutic intervention... - Cathepsin B: an alternative protease for the generation of an aggrecan 'metalloproteinase' cleavage neoepitopeJ S Mort
Joint Diseases Laboratory, Shriners Hospital for Children and Department of Surgery, McGill University, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6
Biochem J 335:491-4. 1998..We show that the combined endo- and exopeptidase activities of the cysteine protease, cathepsin B, also generate this epitope, suggesting that it should no longer be considered as an exclusive marker of metalloproteinase activity... - Articular cartilage and changes in arthritis: matrix degradationJ S Mort
Joint Diseases Laboratory, Shriners Hospital for Children, Montreal, Quebec, Canada
Arthritis Res 3:337-41. 2001..Antineoepitope antibodies that recognize the cleavage products of collagen and aggrecan generated by these enzymes are now available and are being used to detect the sites of action and to quantitate degradation products... - The use of cleavage site specific antibodies to delineate protein processing and breakdown pathwaysJ S Mort
Joint Diseases Laboratory, Shriners Hospital for Children, Montreal, Quebec, Canada
Mol Pathol 52:11-8. 1999.... - Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats ages 0-21 days: I. Two groups of proteinases cleave the core protein of aggrecanE R Lee
Electron Microscopy Unit, Shriners Hospitals for Children, Montreal, Quebec, Canada
Dev Dyn 222:52-70. 2001.... - Immunolocalization of the cleavage of the aggrecan core protein at the Asn341-Phe342 bond, as an indicator of the location of the metalloproteinases active in the lysis of the rat growth plateE R Lee
Electron Microscopy Unit, Shriners Hospital for Children, Montreal, Quebec, Canada
Anat Rec 252:117-32. 1998..The site where metalloproteinases exert their main lytic activity is a thin layer of matrix separating central from peripheral matrix... - Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegmentR Coulombe
Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec
EMBO J 15:5492-503. 1996.... - Soluble recombinant neprilysin induces aggrecanase-mediated cleavage of aggrecan in cartilage explant culturesA Chevrier
Biomedical and Chemical Engineering, Ecole Polytechnique, Station Centre-ville, Montreal, Quebec H3C 3A7, Canada
Arch Biochem Biophys 396:178-86. 2001..These results suggest that NEP is present as a transmembrane enzyme on articular chondrocytes where it can cleave regulatory peptides and lead to the induction of aggrecanase... - Optimization of detergents for the assay of cathepsins B, L, S, and KJ C Krupa
Department of Surgery, McGill University, Montreal, Quebec, Canada
Anal Biochem 283:99-103. 2000..Overall, the results indicate that Chaps is the optimal detergent for use with this family of enzymes... - Involvement of ADAMTS5 and hyaluronidase in aggrecan degradation and release from OSM-stimulated cartilageM Durigova
Shriners Hospital or Children and McGill University, Montreal, Quebec H3G 1A6, Canada
Eur Cell Mater 21:31-45. 2011..Compared to other catabolic cytokines, OSM exhibits a unique potential at degrading the proteoglycan aggregate, by promoting early robust aggrecanolysis, primarily through the action of ADAMTS5, and hyaluronan degradation... - Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitroR Menard
Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada
J Biol Chem 273:4478-84. 1998..However, the bimolecular reaction can be attributed to intermolecular processing of the zymogen... - Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritisT Vinardell
Departement des Sciences Cliniques, Faculte de Medecine Veterinaire, Universite de Montreal, St Hyacinthe, Quebec, Canada
Osteoarthritis Cartilage 17:375-83. 2009..This exposes a neoepitope that can now be identified by specific antibodies. The aim of this study was to obtain evidence suggesting a role for CK in naturally occurring equine OA in both lesional and peri-lesional regions... - Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient miceG Valverde-Franco
J T N Wong Laboratories for Mineralized Tissue Research, and Centre for Bone and Periodontal Research, McGill University, 740 Avenue Dr Penfield, Montreal H3A 1A4, Quebec, Canada
Hum Mol Genet 15:1783-92. 2006..These results identify Fgfr3 signaling as a potential target for intervention in degenerative disorders of cartilage metabolism... - The cleavage of biglycan by aggrecanasesL I Melching
Shriners Hospital for Children, McGill University, Montreal, Quebec, Canada
Osteoarthritis Cartilage 14:1147-54. 2006.... - Characterization of an ADAMTS-5-mediated cleavage site in aggrecan in OSM-stimulated bovine cartilageM Durigova
Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, Quebec H3G 1A6, Canada
Osteoarthritis Cartilage 16:1245-52. 2008.... - Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin MM Durigova
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, Quebec, Canada
Osteoarthritis Cartilage 16:98-104. 2008..To investigate the potential synergistic and differential effects of cytokine combinations on proteoglycan aggregate catabolism in cartilage... - Link protein has greater affinity for versican than aggrecanShuiliang Shi
Joint Diseases Laboratory, Shriners Hospitals for Children, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6
J Biol Chem 279:12060-6. 2004..These observations suggest that link protein may function as a stabilizer of the interaction, not only between aggrecan and hyaluronan in cartilage, but also between versican and hyaluronan in many tissues... - Age-related changes in fibromodulin and lumican in human intervertebral discsR Sztrolovics
Joint Diseases Laboratory, Shriners Hospital for Children, Montreal, Quebec, Canada
Spine (Phila Pa 1976) 24:1765-71. 1999..CONCLUSIONS: Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue... - Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregionM Cygler
Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada
Structure 4:405-16. 1996..The propeptides are potent inhibitors of their parent proteases. Although the proregion binding mode has been elucidated for all other protease classes, that of the cysteine proteases remained elusive... - Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats aged 0-21 days: II. Two proteinases, gelatinase B and collagenase-3, are implicated in the lysis of collagen fibrM A Davoli
Electron Microscopy Unit, Shriners Hospitals for Children, Montreal, Quebec, Canada
Dev Dyn 222:71-88. 2001.... - Production of antibodies against degradative neoepitopes in aggrecanJohn S Mort
Joint Diseases Laboratory, Shriners Hospital for Children, and Departments of Surgery and Medicine, McGill University, Montreal, Quebec, Canada
Methods Mol Med 100:237-50. 2004..Limitations associated with the use of antipeptide antibodies to study authentic protein neoepitopes are discussed... - The characterization of versican and its message in human articular cartilage and intervertebral discRobert Sztrolovics
Shriners Hospital for Children, Montreal, Que, Canada
J Orthop Res 20:257-66. 2002..The increased presence of versican in the disc relative to articular cartilage may suggest a more pronounced functional role for this proteoglycan, particularly in the nucleus pulposus... - Variations in aggrecan structure modulate its susceptibility to aggrecanasesPeter J Roughley
Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6
Biochem J 375:183-9. 2003..Thus, for aggrecan cleavage by aggrecanases, variations in cleavage efficiency exist with respect to the species and age of the animal from which the aggrecan is derived and the type of aggrecanase being used... - The structure and degradation of aggrecan in human intervertebral discPeter J Roughley
Genetics Unit, Shriners Hospital for Children, Montreal, QC, Canada
Eur Spine J 15:S326-32. 2006..The origin and spectrum of disc proteoglycan heterogeneity is the same in both the annulus fibrosus and nucleus pulposus... - Protease analysis by neoepitope approach reveals the activation of MMP-9 is achieved proteolytically in a test tissue cartilage model involved in bone formationEunice R Lee
Electron Microscopy Unit, Joint Diseases Laboratory, Shriners Hospital for Children, and Division of Surgical Research, Department of Surgery, McGill University, Montreal, Quebec, H3G 1A6, Canada
J Histochem Cytochem 54:965-80. 2006..This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials... - Neoepitopes reveal the features of type II collagen cleavage and the identity of a collagenase involved in the transformation of the epiphyses anlagen in developmentEunice R Lee
Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada
Dev Dyn 238:1547-63. 2009..The collective findings reveal that COL2 is attacked at the afore-described susceptible peptide bond at the surface of cartilage canals and, that MMP-13 cleaves it. Developmental Dynamics 238:1547-1563, 2009. (c) 2009 Wiley-Liss, Inc... - Increased collagen and aggrecan degradation with age in the joints of Timp3(-/-) miceSolmaz Sahebjam
Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada
Arthritis Rheum 56:905-9. 2007..To investigate the in vivo effect of an imbalance between metalloproteinases and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in mouse articular cartilage... - Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilageValeria M Dejica
Joint Diseases Laboratory, Shriners Hospitals for Children, 1529 Cedar Ave, Montreal, Quebec, H3G1A6, Canada
Am J Pathol 173:161-9. 2008..These data suggest that cathepsin K is involved in the cleavage of type II collagen in human articular cartilage in certain OA patients and that it may play a role in both OA pathophysiology and the aging process... - Rat procathepsin B. Proteolytic processing to the mature form in vitroA D Rowan
Joint Diseases Laboratory, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada
J Biol Chem 267:15993-9. 1992..This work has also shown that the processing of procathepsin B to a single-chain form can be an autocatalytic process, in at least an intermolecular manner... - Identification of UDP-N-acetylglucosamine-phosphotransferase-binding sites on the lysosomal proteases, cathepsins A, B, and DK E Lukong
Service de Genetique Medicale, Hopital Sainte Justine, Universite de Montreal, Quebec, Canada
Biochemistry 38:73-80. 1999..We propose that recognition and catalytic sites of the phosphotransferase are located on different subunits, therefore, providing an effective mechanism for binding and phosphorylation of lysosomal proteins of different molecular size... - Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritisMandana Mahmoodi
Joint Diseases Laboratory, Shriners Hospital for Children, 1529 Cedar Ave, Montreal, Quebec, Canada H3G 1A6
Am J Pathol 166:1733-40. 2005..No difference in Safranin O staining or aggrecan cleavage site neoepitope abundance was seen. Thus, in inflammatory joint disease TIMP-3 likely dampens the inflammatory response of TNF-alpha by reducing ADAM17 activity... - Hyaluronate degradation as an alternative mechanism for proteoglycan release from cartilage during interleukin-1beta-stimulated catabolismRobert Sztrolovics
Joint Diseases Laboratory, Shriners Hospital for Children, McGill University, Montreal, Quebec, Canada H3G 1A6
Biochem J 362:473-9. 2002..It is likely that both mechanisms contribute to cartilage metabolism in normal physiology and pathology... - Insect cell conditioned medium contains an endoglycosidase able to liberate chondroitin sulfate chains from aggrecanPeter J Roughley
Shriners Hospital for Children and Department of Surgery, McGill University, Montreal, Quebec, Canada
Matrix Biol 24:371-5. 2005..It may also represent an impediment to such research when baculovirus systems are used to generate recombinant proteoglycans... - Loss of responsiveness to IGF-I in cells with reduced cathepsin L expression levelsR Navab
Department of Surgery, McGill University, Montreal, Quebec, Canada
Oncogene 27:4973-85. 2008..The results demonstrate that cathepsin L expression levels regulate cell responsiveness to IGF-I and thereby identify a novel function for cathepsin L in the control of the tumorigenic/metastatic phenotype... - The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinasesNadia Nour
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
Mol Biol Cell 16:5215-26. 2005..In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase... - S2' substrate specificity and the role of His110 and His111 in the exopeptidase activity of human cathepsin BJoanne C Krupa
Joint Diseases Laboratory, Shriners Hospital for Children, 1529 Cedar Avenue, , , Canada
Biochem J 361:613-9. 2002..9 kJ/mol (3.3 kcal/mol). These studies showed that cathepsin B is optimized to act as an exopeptidase, cleaving dipeptides from protein substrates in a successive manner, because of its relaxed specificity in P2' and its other subsites... - Quantitative bead assay for hyaluronidase and heparinase IJoanne C Krupa
Joint Diseases Laboratory, Shriners Hospital for Children, Montreal, Que, Canada
Anal Biochem 319:280-6. 2003..The assay is suitable for detecting the presence of these glycosaminoglycan-degrading enzymes in cell lysates, extracts, or purified fractions, for quantifying their amounts, and for investigating the activity of potential inhibitors... - Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate estersMireille N Vankemmelbeke
Division of Genomic Medicine, University of Sheffield Medical School, Sheffield Children's Hospital, Stephenson Wing, D-Floor, UK
Eur J Biochem 270:2394-403. 2003.... - The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee jointManojkumar Valiyaveettil
Department of Biomedical Engineering, Lerner Research Institute and Orthopaedic Research Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Connect Tissue Res 46:83-91. 2005..Thus, differences in the concentration, gene expression, and spatial distribution of aggrecan constitute another molecular distinction between hyaline cartilage and fibrocartilage of the knee... - Crystal structure of the parasite protease inhibitor chagasin in complex with a host target cysteine proteaseAnna Ljunggren
Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, SE 221 85 Lund, Sweden
J Mol Biol 371:137-53. 2007..This information will aid in the development of synthetic inhibitors for use as potential drugs for the treatment of Chagas disease... - Cartilage-specific constitutive expression of TSG-6 protein (product of tumor necrosis factor alpha-stimulated gene 6) provides a chondroprotective, but not antiinflammatory, effect in antigen-induced arthritisTibor T Glant
Rush University, Rush Presbyterian St Luke s Medical Center, Chicago, Illinois 60612, USA
Arthritis Rheum 46:2207-18. 2002..To study the chondroprotective effect of constitutively expressed TSG-6 protein (tumor necrosis factor alpha-induced protein 6; Tnfip6) in cartilage, using antigen-induced arthritis (AIA) in mice... - Measurement of glycosaminoglycan release from cartilage explantsJohn S Mort
Methods Mol Med 135:201-9. 2007..Two approaches for GAG assay are described, with special attention being paid to the advantages and limitations of each method... - Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin BIzabela Redzynia
Faculty of Biotechnology and Food Sciences, Technical University of Lodz, 90 924 Lodz, Poland
J Biol Chem 283:22815-25. 2008..The chagasin-cathepsin B complex provides a structural framework for modeling and design of inhibitors for cruzipain, the parasite cysteine protease and a virulence factor in Chagas disease... - Expression and localization of cathepsin k in adult rat sertoli cellsMatthew D Anway
Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Biol Reprod 70:562-9. 2004..If true, this might explain the fertility of furless mice. Further, the results suggest that cathepsin K, in both its secreted and lysosomal forms, may play a role in the degradation of Sertoli cell residual bodies...