Mice resistant to collagen degradation teach us about skeletal development and arthritis

• 
  Project Leader
  Professor Amanda Fosang

  amanda.fosang@mcri.edu.au

Project Details

Type II collagen is an important structural molecule that gives cartilage its shape and tensile strength. As arthritis progresses, collagen is destroyed by collagenases, causing irreversible cartilage damage. We made mice with collagen II that resists destruction by collagenases and discovered that these mice were protected against cartilage erosion in experimental arthritis. The data suggest that therapies aimed at protecting the collagen scaffold in arthritis will be more effective than therapies aimed at preventing aggrecan loss alone.

The ‘collagenase-resistant’ mice also have fascinating skeletal abnormalities. We established a skeletal development program to determine why the growth of long bones is delayed in these mice. We are now focussed on understanding the mechanism underlying this phenotype and the possible role of specfic collagen fragments.

Researchers

• Ms Suzanne Golub, Research Assistant
• Ms Karena Last, Research Assistant
• Ms Jia-Xi Han, Research Assistant
• Ms Lynette Ong, PhD Student
• Dr Heather Stanton, Research Officer/Administrator

Collaborators

• Professor Hideaki Nagase, Kazuhiro Yamamoto & Dr Linda Troeberg, Kennedy Institute of Rheumatology, Oxford, UK
• Dr Anne-Marie Malfait & Dr Rachel Miller, Rush University, Chicago, USA
• Prof Alan Grodzinsky, Massachusetts Institute of Technology, Boston, USA
• Prof Virginia Kraus, Duke University, USA
• Prof Anders Aspberg, University of Copenhagen, Denmark
• Prof Frank Beier, University of Western Ontario, Canada
• Dr Paul Holden, Oregon Health & Science University, Oregon, USA
• Prof Danny Chan, University of Hong Kong, China
• A/Prof Philip Sutton, MCRI
• Prof John Bateman, MCRI
• A/Prof Shireen Lamande, MCRI
• Dr Marc Seal, Royal Children’s Hospital
• Prof David Jackson, University of Melbourne
• Prof Eleanor Mackie, University of Melbourne
• A/Prof Natalie Sims, St Vincent’s Institute, Melbourne
• Prof Chris Little, University of Sydney, NSW

Funding

• USA Department of Defense
• National Health & Medical Research Council  
• Australian Research Council