This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Molecular Interactions of the pericellular matrixThe extracellular matrix (ECM) of tissues is composed of water, hyaluronic acid and collagen. Within the matrix, numerous growth factors and enzymes carry out their functions as cells respond to their local environment. Cartilage consists of 5% cells and 95% ECM by volume, and is therefore a good model system to study ECM. In addition the coordination of signaling events that take place as the tissue first develops, and is then replaced by bone, represent a challenge to study. The pericellular matrix is that portion of the ECM that is immediately associated with the cells, and mediates events that take place at the surface of cells such as cell matrix interactions and ligand-receptor interactions. Cells modify their local environment in response to biochemical and mechanical signals.We hypothesize that specific molecular constituents of the pericellular matrix determine the nature of the immediate environment of the cell. The focus of this proposal is to study the unique globular domain of the collagen types V and XI.
The specific aims i nclude: 1) To culture chondrocyte cells under conditions that allow the accumulation of the pericellular matrix; 2) To perturb the pericellular matrix using metalloproteinase inhibitors and other methods; and 3) To determine the effect of these perturbations on the structure of the pericellular matrix.
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