Raymond Purves Bone and Joint Research Laboratory

Within: Institute of Bone and Joint Research, Kolling Institute of Medical Research

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Overview of research program

The Raymond Purves Bone and Joint Research Laboratories research is focused on understanding the pathobiology and underlying molecular mechanisms of diseases of the musculoskeletal system. Our group studies osteoarthritis, disc disease and more recently tendon and ligament disorders. The laboratories have a long history of using animal models to study disease and recently have utilised genetically modified mice to investigate mechanisms and treatment of cartilage breakdown in arthritis. A number of ongoing projects funded by external granting bodies and industry include:

  • The role of perlecan, a heparin sulphate proteoglycan, in tensile and weight–bearing musculoskeletal tissues in health and disease
  • Calcification of the intervertebral disc
  • Molecular and mechanical changes associated with intervertebral disc degeneration
  • Mechanisms of tendon degeneration – molecular and biochemical causes
  • Treating tendon degeneration with mesenchymal stem cells
  • Small leucine rich repeat proteoglycans (SLRPs) in cartilage intervertebral disc and tendon diseases
  • Investigating the mechanisms of meniscal degeneration in the knee
  • The role of activated protein C in MMP activation in cartilage degeneration in arthritis
  • The role of ADAMTS enzymes in arthritis
  • Transcriptional profiling to investigate the mechanisms of initiation and progression of cartilage degeneration in osteoarthritis
  • Investigating the role of various enzymes and their activators in cartilage breakdown in arthritis using genetically modified mice
  • Longitudinal studies on biochemical, biomechanical and histological properties of cartilage, subchondral bone and synovial fluid in an ovine model of osteoarthritis
  • Use of stem cells to treat arthritis

Major funding sources

Competitive national/international funding bodies

  • National Health and Medical Research Council (NHMRC)
  • The Hillcrest Foundation
  • Australian Orthopaedic Association
  • Arthritis Australia
  • Rebecca Cooper Medical Research Foundation

Commercial funding bodies

  • Pfizer Inc
  • Fidia Farmaceutici SpA
  • Mesoblast Australia

Selected publications

These recent papers demonstrate the scope of research interests of our laboratories.

Little CB, Meeker CT, Hembry R, Sims, N, Last K, Golub S, Fosang AJ. Matrix metalloproteinases are not essential for aggrecan turnover in normal skeletal growth and development. Mol Cell Biol 2005;25:3388-3399.

Stanton H, Rogerson FM, East CJ, Golub SB, Little CB, Lawlor KE, Farmer PJ, Fourie AM, Meeker CT, Fosang AJ. ADAMTS-5 is the major aggrecanase in mouse cartilage, in vivo and in vitro. Nature 2005;434:648-652.

Young AA, Smith MM, Smith SM, Cake MA, Ghosh P, Read RA, Melrose J, Sonnabend DH, Roughley PJ, Little CB. Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis. Arthritis Res Ther 2005;7:R852-861.

Melrose J, Roughley PJ, Knox S, Smith SM, Lord M and Whitelock JM (2006). The Structure, Location and Function of Perlecan, a Prominent Pericellular Proteoglycan of Foetal, Postnatal and Mature Hyaline Cartilages. J Biol Chem Dec 1;281(48):36905-14.

Little CB, Meeker CT, Golub SB, Lawlor KE, Farmer PJ, Smith SM, Fosang AJ. Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair. J Clin Invest. 2007;117:1627-1636

Melrose J, Smith SM, Fuller ES, Young AA, Roughley PJ, Dart A, Little CB. Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling In experimentally injured ovine intervertebral discs. Eur Spine J. 2007;16:2193-205

Smith MM, Sakarai G, Smith SM, Young AA, Melrose J, Stewart C, Appleyard RC, Peterson JL, Gillies M, Dart A, Sonnabend DH, Little CB. Modulation of aggrecan and ADAMTS expression in endon pathology induced by altered strain. Arthritis Rheum. 2008;58:1055-66

Melrose J, Fuller ES, Roughley PJ, Smith MM, Kerr B, Hughes CE, Caterson B, Little CB. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis Res Ther. 2008 Jul 14;10(4):R79

MM Smith, M. A. Cake, P. Ghosh, A. Schiavanato, R. A. Read, D. Burkhardt, C. B. Little. Modulation of synovial pathology in an ovine model of osteoarthritis by intra-articular administration of hyaluronan (Hyalgan®) and an amide derivative of hyaluronan, HYADD4-4®. Rheumatology (Oxford). 2008;47:1172-8. (4.05)

Jackson M, Smith MM, Smith SM, Xue M, Jackson C, Little CB. The role of activated protein C (APC) in MMP activation and collagenolysis in cartilage. Arthritis Rheum In press Nov 2008.

Major collaborations

Today, successful medical research does not occur in isolated laboratories but depends upon national and international collaborations. The Raymond Purves Bone and Joint Research Laboratories has strong collaborations with a number of groups nationally and internationally including:

  • A/Prof. Amanda Fosang, Arthritis Research Group, Dept of Paediatrics, Melbourne University
  • Prof. John Bateman, Musculoskeletal Biology, Murdoch Childrens Research Institute
  • Dr Hala Zreiqat, Tissue Engineering & Biomaterials Research Unit, School of AMME, University of Sydney
  • Prof. John Whitelock, Graduate School of Biomedical Engineering, UNSW
  • Prof. Peter Roughley, McGill University, Montreal, Canada
  • Prof. Bruce Caterson, Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University, Cardiff, UK
  • Dr Tony Hayes, Confocal Microscopy Unit, School of Biosciences, Cardiff University, Cardiff, UK