Endothelial cells have been implicated in several systems as inducing differentiation and migration of cells during wound healing. Considerable angiogenesis occurs prior to dentin bridge formation and it is the perivascular pulpal fibroblasts that are stimulated to differentiate into odontoblasts after a pulpal exposure. These findings are suggestive of more than a simple nutritive relationship. The proposed study will investigate the interactions of endothelial cells with pulpal fibroblasts differentiating into odontoblasts during wound healing in the dental pulp. A cell line will be generated from the dental pulp fibroblasts of a mouse strain previously shown to allow spontaneous generation of well- characterized endothelial cell lines. This cell line will be cocultured with an existing endothelial cell line to produce an in vitro model system to study the influence of endothelial cells on pulpal fibroblast differentiation. One specific endothelial cell adhesion receptor, VCAM, is involved in cell-cell interactions between endothelial cells and other cell types. The modulation of VCAM expression during coculture and the influence this has on the interaction of the cell lines will be studied. The results from these in vitro investigations will be confirmed using an in vivo pulp capping model to investigate the possible functional significance of VCAM modulation during endothelial induction of fibroblast cytodifferentiation. These studies will have the dual role of investigating an important mechanism in dental wound healing and generating two novel model systems that can be used to study the mechanism of other pulpal responses.
