Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon

Neovascularization is an important and prominent feature of tendon healing that contributes to wound repair and potentially to adhesion formation. To define the location of cell populations that recruit and organize the angiogenic response during early healing of flexor tendon, we examined the gene expression pattern of the prototypic angiogenic factor, vascular endothelial growth factor, at and around the tenorrhaphy site in a canine model of flexor tendon repair. In situ hybridization with radiolabeled antisense riboprobes was used to identify tendon cell populations that contribute to the neovascularization process by expressing vascular endothelial growth factor and to relate this cell population to the previously described cell populations that participate in matrix synthesis (express type alpha1(I) collagen) and mitotic renewal (express histone H4). The majority of cells (approximately 67%) within the repair site itself express vascular endothelial growth factor mRNA; however, minimal levels accumulate within cells of the epitenon (approximately 10% of cells; p < 0.0002). By contrast, expression of type alpha1(I) collagen and histone H4 does not differ significantly between the epitenon and the repair site (uniformly approximately 30% of cells). Thus, a gradient of cell populations expressing vascular endothelial growth factor exists in the repairing tendon. These data suggest a potential contribution of cells within the repair site to the organization of angiogenesis during the early postoperative phase of tendon healing.