Extracellular matrix - immune system interaction

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The extracellular matrix (ECM) of the bone marrow is derived from a secreted specialized matrix in growth plate cartilage. Changes in the composition of the cartilage ECM early in development can affect the organization of the ECM in the bone marrow to impair the development and function of bone marrow derived immune cells, but little is known about the underlying mechanisms. Collagen IX is expressed in cartilage to stabilize the ECM. Our recent findings show that lack of collagen IX transiently alters the composition of the trabecular ECM in the postnatal bone marrow to impair myeloid progenitor cell differentiation in the adult. In the planned project we will identify proteins of the ECM in collagen IX deficient mice that can induce long term changes in hematopoiesis. Protein interaction studies will be used to characterize the interplay of these proteins with the cartilage ECM and extracellular signaling molecules, while cell culture differentiation assays and infection studies in collagen IX deficient mice will define their influence on hematopoiesis and the immune response. The analysis will characterize the priming effects of cartilage ECM components on immune cell differentiation and function. Moreover, the results may provide a general understanding of ECM induced immune-related diseases of the skeletal system.