Localization of specific binding sites for 125I-TGF-beta1 to fenestrated endothelium in bone and anastomosing capillary networks in enamel organ suggests a role for TGF-beta1 in angiogenesis

Previous studies have shown endothelial cells to be a major target for endocrine TGF-beta in several soft tissues in the normal growing rat. The potent effect of TGF-beta1 on bone formation prompted us to analyze in detail the localization of specific binding sites for endocrine TGF-beta in hard tis...

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Bibliographic Details
Published in:Calcified tissue international 2001-05, Vol.68 (5), p.304-315
Main Authors: Dickson, K M, Bergeron, J J, Philip, A, O'Connor-McCourt, M, Warshawsky, H
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Autoradiography
Binding Sites
Capillaries - metabolism
Capillaries - ultrastructure
Enamel Organ - blood supply
Enamel Organ - metabolism
Enamel Organ - ultrastructure
Endothelium, Vascular - metabolism
Endothelium, Vascular - ultrastructure
Incisor
Iodine Radioisotopes
Mice
Microscopy, Electron
Neovascularization, Physiologic - physiology
Rats
Tibia - metabolism
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta1
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Summary:Previous studies have shown endothelial cells to be a major target for endocrine TGF-beta in several soft tissues in the normal growing rat. The potent effect of TGF-beta1 on bone formation prompted us to analyze in detail the localization of specific binding sites for endocrine TGF-beta in hard tissues. At 2.5 minutes after injection of 125I-TGF-beta1, specific binding, as demonstrated by quantitative radioautography, was localized to fenestrated endothelium participating in angiogenesis in the vascular invasion region of the growth plate in bone as well as to anatomizing capillary networks in the maturation zone of the enamel organ. At 15 minutes after injection, the bound ligand was internalized into endocytic vesicles of endothelial cells. In bone, quantitation revealed significant differences in receptor density between endothelia undergoing proliferation vs those in a state of elongation and anastomosis with neighboring endothelial cells. In the rat incisor, specific binding of 125I-TGF-beta1 to endothelium correlated with increased formation of anastomotic capillary networks. These studies identify differential specific binding sites of 125I-TGF-beta1 in angiogenically active endothelium, providing an important link between TGF-beta1, the endothelium, and hard tissue development.
ISSN:0171-967X