Functional effects of antibodies to collagen on cartilage synthesis and degradation

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/143549

Funding Status
Closed

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Funded Activity Summary

It has been shown that antibodies to collagen type II in cartilage occur in ~70% of patients with early rheumatoid arthritis, suggesting that autoimmunity to cartilage collagen may play a part in the devleopment of this destructive arthritis. An animal model widely used as a model of human RA is the disease collagen induced arthritis (CIA). It is induced by immunisation of mice with collagen II; antibodies to collagen II are critical for the development of CIA. However not all such antibodies are disease-associated. There may be particular regions on the collagen molecule where antibody-binding causes damage. This project is based on the hypothesis that antibodies to collagen type II, which transfer arthritis in mice, are those that react specifically with regions of the collagen fibrils that are crucial for cartilage stability and function. We plan to test this hypothesis in an in vitro system using cultured cartilage. We predict, based on our preliminary data, that antibodies to collagen II from mice with CIA will interfere with the normal assembly and structure of cartilage. We will test this by adding antibodies under precisely defined conditions to cultured cartilage, and analysing the matrix that is synthesised. The study would then be extended to RA with a comparison of the regions of collagen II that react with antibodies of mouse and human origin. Showing that antibodies to collagen II are directly destructive, allowing for an understanding of their site and mode of action, would greatly advance our understanding of the cause of RA and would lead to more effective forms of treatment.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $227,036.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Rheumatology And Arthritis

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Autoimmunity | Cartilage damage | Cartilage matrix biology | Collagen antibodies | Collagen induced arthritis | Inflammatory arthritis | Rheumatoid arthritis

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