Inhibition of tubular morphogenesis in human microvascular endothelial cells by co-culture with chondrocytes and involvement of transforming growth factor β: a model for avascularity in human cartilage

Abstract

Tube formation in collagen gel was induced in human omental microvascular endothelial (HOME) cells in the presence of epidermal growth factor (EGF) or transforming growth factor-α (TGF-α). TGF-α enhanced the expression of the tissue plasminogen activator (t-PA) gene, whereas TGF-β increased the expression of the PA inhibitor-1 (PAI-1) gene and inhibited that of the t-PA gene. TGF-β inhibited the tube formation of HOME cells in type I collagen gel that was enhanced in response to TGF-α. We have recently established an angiogenesis model in vitro in which vascular endothelial cells on type I collagen gel in an inner chamber are co-cultured with other types of cells in an outer chamber. Here we examined whether the EGF/TGF-α-induced tube formation in HOME cells was modulated by human chondrocytes co-culture in the outer chamber. TGF-α-dependent tube formation of HOME cells was inhibited when human chondrocytes were co-cultured in the outer chamber. This chondrocyte-induced inhibition of tube formation was partly abrogated by co-administration of anti-TGF-β antibody. These findings suggest that TGF-β is partly involved in the human chondrocyte-dependent inhibition of tube formation by human microvascular endothelial cells. This is the first model system demonstrating that avascularity of human chondrocytes is partly due to the TGF-β family produced from them.