Localization of specific binding sites for I-125-TGF-beta 1 to fenestratedendothelium in bone and anastomosing capillary networks in enamel organ suggests a role for TGF-beta 1 in angiogenesis

Previous studies have shown endothelial cells to be a major target for endo crine TGF-beta in several soft tissues in the normal growing rat [26]. The potent effect of TGF-beta1 on bone formation prompted us to analyze in deta il the localization of specific binding sites for endocrine TGF-beta in har d tissues. At 2.5 minutes after injection of I-125-TGF-beta1, specific bind ing, as demonstrated by quantitative radioautography, was localized to fene strated endothelium participating in angiogenesis in the vascular invasion region of the growth plate in bone as well as to anatomizing capillary netw orks in the maturation zone of the enamel organ. At 15 minutes after inject ion, the bound ligand was internalized into endocytic vesicles of endotheli al cells. In bone, quantitation revealed significant differences in recepto r density between endothelia undergoing proliferation vs those in a state o f elongation and anastomosis with neighboring endothelial cells. In the rat incisor, specific binding of I-125-TGF-beta1 to endothelium correlated wit h increased formation of anastomotic capillary networks. These studies iden tify differential specific binding sites of I-125-TGF-beta1 in angio-genica lly active endothelium, providing an important link between TGF-beta1, the endothelium, and hard tissue development.