In summary, our studies suggest that TNF-alpha-induced N-SMase activation and production of ceramide is required to activate the apoptosis pathway in human osteosarcoma cells.
To determine the molecular mechanisms involved in the regulation of gene expression of osteoblast-like cells, we analyzed the effects of TNF-alpha on the human osteosarcoma cell line Saos2.
The results of these studies showed that TNF-a and okadiac acid caused dose- and time-dependent increases in apoptosis in the SaOS-2 cells (r = 0.78 for doses of TNF-a and r = 0.93 for doses of okadiac acid, P <0.005 for each), with associated decreases in cell layer protein (P <0.05 for each) and concomitant increases in the release of sALP activity (e.g., r = 0.89 for TNF-a and r = 0.75 for okadiac acid, P <0.001 for each).
Induction and stimulation of 92-kDa gelatinase/type IV collagenase production in osteosarcoma and fibrosarcoma cell lines by tumor necrosis factor alpha.