Inhibition of tubular morphogenesis in human microvascular endothelial cells by co-culture with chondrocytes and involvement of transforming growth factor beta: a model for avascularity in human cartilage.
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-alpha (TGF-alpha). TGF-alpha enhanced the expression of the tissue type plasminogen activator (t-PA) gene, whereas TGF-beta increased the expression of the PA inhibitor-1 (PAI-1) gene and inhibited that of the t-PA gene. TGF-beta inhibited the tube formation of HOME cells in type I collagen gel that was enhanced in response to TGF-alpha. 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-alpha-induced tube formation in HOME cells was modulated by human chondrocytes co-culture in the outer chamber. TGF-alpha-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-beta antibody. These findings suggest that TGF-beta 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 TGF-beta family produced from them.
Tada
K
K
Department of Orthopedics, Oita Medical University, Japan.
Fukunaga
T
T
Wakabayashi
Y
Y
Masumi
S
S
Sato
Y
Y
Izumi
H
H
Kohno
K
K
Kuwano
M
M
D002356:Cartilage / Q000098:blood supply* / Q000166:cytology / Q000648:ultrastructure; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000737:chemistry*
D016212:Transforming Growth Factor beta