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Dr Christopher B Little
Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research and Department of Orthopaedic and Traumatic Surgery
University of Sydney
Level 5 University Clinic ? B26, Royal North Shore Hospital, St. Leonards, NSW 2065
Email: cblittle@med.usyd.edu.au
Tel: +61-3 9926 7239
Fax: +61-3 9926 6539

The research at the Raymond Purves Labs has focused on degenerative disorders of the musculoskeletal system in three broad areas: 1) joint disease, in particular osteoarthritis; 2) intervertebral disc degeneration; and 3) diseases of tendon/ligament and meniscus. Our interest in all of these tissues has been to investigate the catabolic and anabolic pathways that lead to breakdown in disease. We have studied cartilage, disc and tendon degeneration at the molecular level using in vitro culture models of tissue degradation and we have developed and extensively studied in vivo animal models of osteoarthritis and disc degeneration. Currently, a new surgically induced model of osteoarthritis in mice is being studied, to enable us to use global transcriptional analysis of the molecular changes occurring in early cartilage breakdown.
Much of this previous work has centred on the changes in the synthesis and catabolism of the major extracellular matrix proteoglycan in cartilage, disc and compressed tendon, namely aggrecan. We have used biochemical, molecular and immunological approaches to explore the proteinases responsible for catabolism of aggrecan in normal turnover and disease. Development and use of neoepitope antibodies that specifically recognise new amino- or carboxy-termini in cleaved but not intact proteins, has proven invaluable for determining the role of MMPs and ADAMTS enzymes in aggrecan proteolysis. We have now initiated similar studies to examine the proteinases responsible for and the consequences of, breakdown of the small leucine-rich repeat proteoglycans (SLRPs) in cartilage, disc and tendon in disease.
Dr. Amanda Fosang, Melbourne University, Australia
Professor John Bateman, Melbourne University, Australia
Professor Bruce Caterson, Cardiff University, UK
Professor Dick Heinegard, University of Lund, Sweden
Dr. John Mort, University of Montreal, Canada
Dr. Peter Roughley, University of Montreal, Canada
Dr. Carl Flannery, Wyeth Pharmaceuticals, Boston, USA
Dr. Mike Janusz, Procter & Gamble, Mason, USA
Flannery CR, Little CB, Caterson B and Hughes CE. Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes. Matrix Biol. 1999;18:225-237

Rees SG, Flannery CR, Little CB, Hughes CE, Caterson B and Dent CM. Catabolism of aggrecan, decorin and biglycan in tendon. Biochem. J. 2000;350:181-188

Melrose J, Smith S, Rodgers K, Little C, Burkhardt D and Ghosh P. Immunolocalisation of BPTI-like serine proteinase inhibitory proteins in mast cells, chondrocytes and intervertebral disc fibrochondrocytes of ovine and bovine connective tissues. An immunohistochemical and biochemical study. Histochem. Cell. Biol. 2000;114:137-146

Little CB, Hughes CE, Curtis CL, Jones SA, Caterson B, Flannery CR. Cyclosporin A inhibition of aggrecanase-mediated proteoglycan catabolism in articular cartilage. Arthritis Rheum. 2002;46:124-129

Little CB, Hughes CE, Curtis CL, Janusz MJ, Bohne R, Wang-Weigand S, Taiwo YO, Otterness IG, Mitchell PG, Flannery CR and Caterson B. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. Matrix Biol. 2002;21:271-288

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