The role of a novel extracellular matrix protein, WARP, in cartilage development, function and pathology

Funded Activity Summary

The environment outside all cells is absolutely essential for normal growth and development. In order to undertand many disease and developmental processes it is critical that we acquire a detailed understanding of the various extracellular matrix components and how they interact to form a functional extracellular matrix. We recently discovered a new extracellular matrix protein which we have named WARP for von Willebrand factor A-domain-related protein. Our experiments demonstrate that WARP is an important constituent of the three-dimensional structure of the extracellular matrix of the articular surface of cartilage. We can show that WARP forms large-scale structures in tissue culture experiments and in extracts from mouse cartilage, and we have some new data which suggests that WARP interacts specifically with collagen II, a large and quantitatively major component of cartilage. We will explore the function of WARP in cartilage and include in vitro experiments that will reveal information about its distribution, tissue forms, and interactions with other extracellular matrix components (PART 1). To define the in vivo role of WARP we will generate a WARP gene knockout mouse (PART 2). These experiments will provide valuable information about the structure of the cartilage in the joint on the surface of bone and in particular the function of WARP in this structure. Since WARP is at the articular cartilage surface we asked whether WARP is lost in cartilage degeneration. In cartilage tissue grown in vitro under conditions that promote cartilage degradation, WARP is fragmented and released from the cartilage surface. We will explore this further in in vitro and in vivo models of cartilage breakdown (PART 3). Thus, in addition to promoting a new understanding of cartilage structure WARP has the exciting potential to become a specific biomarker for arthritis a major joint degenerative disease with high medical and financial cost to the community.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $482,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Interactions (Incl. Adhesion, Matrix, Cell Wall)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

arthritis | cartilage | cartilage degradation | extracellular matrix | joint disease | skeletal disease

Related Links