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.
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