2006 AFAR Research Grant: Aging and S100A4 in Cartilage

Please give a brief summary of your AFAR research project.
The major goals are to examine the function and regulation of S100A4 in cartilage and to define the cell-signaling pathways that regulate the production of MMP-13 in cartilage in response to S100A4 stimulation.

What problems are you addressing and what specific questions will your research seek to answer?
Osteoarthritis (OA) is characterized by progressive destruction of cartilage. Although many factors can lead to development of OA, the primary risk factor is aging. In our preliminary studies, we found that the expression of S100A4 is up regulated in OA cartilage. The goal of the project is to examine the molecular mechanisms that modulate the expression and function of S100A4 in cartilage with age and in development of OA.

What aspects of your project are most interesting from a scientific point of view?
S100A4 is a low molecular weight, calcium-binding protein that belongs to a family of S100 proteins. Members of this family play an important role in a variety of cellular activities in various cell/tissue types. However, very little is known about their function and regulation in cartilage. Our preliminary studies have established that S100A4 binds to Receptor for Advance Glycation End products (RAGE) and activate an array of signaling molecules. The major goal of the AFAR project is to define RAGE-mediated cell signaling pathways in cartilage with age and linking to development of OA.

What are the implications of your research for age-related diseases and disorders?
The results obtained from this project will provide basic cellular and molecular mechanisms that link aging to the development of OA. The project is directed at the aging aspects, rather than on the disease itself, should provide a novel approach to the disease.

Return to 2006 AFAR Grantees