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Arthritis Research

Arthritis is a major cause of disability in Australia, affecting nearly one in five people. It is not a single disease, but a range of conditions affecting the joints. There is no cure for arthritis, although there are therapies to manage the disease. It is a common misconception that arthritis is associated with ageing, but children are affected as well as adults. Juvenile arthritis commonly goes into remission by early adulthood, but children can be left with restricted joint movement, growth defects due to steroid therapies or skeletal deformities.

The research group studies the molecular events that lead to cartilage, bone and joint destruction in arthritis, focusing primarily on molecules that define cartilage structure, and the enzymes that destroy them. Although there are common patterns of cartilage destruction across all arthritic conditions, there are also specific points of difference at the molecular level. Our group focuses on defining anabolic and catabolic pathways in juvenile arthritis and osteoarthritis (the most common form of arthritis).

Professor Amanda Fosang, Group Leader of Arthritis Research, has 25 years of experience in arthritis-related research. She has an international reputation for excellence in the field and is on the Board of Directors for the Osteoarthritis Research Society International (OARSI).

Group Leaders: 
Group Members: 
Dr Roger Allen
Honorary Research Fellow
Dr Jonathan Akikusa
Honorary Research Fellow
Dr Stephanie Gauci
Postdoctoral Fellow
Hansen Kosasih
PhD student
Lynette Ong
PhD student
Samuel Darby
Masters student

In healthy articulating joints, cartilage lining the long bones absorbs the compressive forces generated by movement and weight-bearing. An intact cartilage matrix is a cornerstone for healthy joints. The cartilage cells maintain a balance between matrix synthesis and matrix degradation, but in arthritic cartilage this balance is disturbed, causing changes in matrix metabolism, either as pathology, or an attempt at repair. In the laboratory, our goal is to understand the pathways and catabolic processes leading to cartilage degradation in health and disease.

The role of an aggrecan 32mer fragment in developing osteoarthritis
The proteoglycan aggrecan is a key component of the cartilage matrix, responsible for enabling weight bearing, by providing compressive resilience. Aggrecan is degraded in early arthritis and we have evidence to suggest that a fragment of aggrecan, the ‘32mer’, might contribute joint damage. We have a project funded by the USA Department of Defense to investigate whether a monoclonal antibody that neutralises 32mer activity will alleviate arthritis resulting from acute joint injury.

Skeletal development and arthritis severity in mice resistant to collagen destruction
Type II Collagen is an important structural molecule that gives cartilage its shape and tensile strength. As arthritis progresses, collagen II is destroyed by collagenases, causing irreversible cartilage damage. We made mice with collagen 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 specific collagen fragments.

An ultrasensitive assay to detect aggrecan degradation products in patient fluidsWe are developing an ultrasensitive ELISA assay for detecting aggrecan degradation products in patient sera and synovial fluids. Using this assay, we will be able to quantitate aggrecan fragments that were previously at the limits of detection. We will be able to build a more detailed picture of how aggrecan is degraded in adult and juvenile arthritis.

Identifying novel cartilage proteins with new functions
We have discovered that cells from mouse joint tissues respond to inflammatory agents by increasing their expression of the vanin-3 (vnn3) gene. Although little is known about vnn3, the related protein vanin-1 is involved in the body’s response to infection, inflammation and tissue damage. We propose that vnn3 will also be important in the response to disease. This project aims to identify the role(s) of vnn3 in modulating cartilage pathology in experimental arthritis and to explore the link between vnn3, arthritis and metabolic disease.  We have made mice deficient in vnn3 and we are using these mice to define the in vivo role of vnn3 in modulating cartilage erosion in experimental arthritis and the possible links with metabolic disease.

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