The role of TNF family members TWEAK and TNF-alpha in bone remodelling

Funded Activity Summary

Bone remodelling, or turnover, is the process by which bone is broken down by osteoclasts and replaced by osteoblasts. Disruption of this process is the cause of many bone-related diseases that affect millions of Australians and countless others worldwide. It is controlled by the complex interactions of a large number of systemic factors (hormones) and locally acting agents, such as chemokines and cytokines, the details of which are not fully understood. Each of these factors, however, is a potential therapeutic target. Pro-inflammatory cytokines, those that are associated with inflammatory diseases such as Rheumatoid Arthritis (RA), are known to have key roles in both the physiology and pathology of bone. TWEAK is a recently described member of the TNF family of cytokines. We have shown that TWEAK is a novel mediator of inflammatory arthritis in mouse model systems and is therefore a likely candidate as a therapeutic target. We now have extensive preliminary data to suggest that TWEAK is involved in human RA, and also in the regulation of normal bone remodelling. TWEAK therefore may be implicated in a wide spread of bone diseases, including osteoporosis. We believe it is of great importance to perform a thorough analysis of TWEAK in bone biology, and we propose to do so.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $566,946.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Orthopaedics

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

bone loss | bone resorption and remodelling | inflammation | joint disease | osteoblast | osteoclast | osteolysis | osteoporosis | rheumatoid arthritis | tumour necrosis factor

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