Glucocorticoid Regulation of Alkaline Phosphatase in the Osteoblastic Osteosarcoma Cell Line ROS 17/2.8*

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Abstract
Dexamethasone increased alkaline phosphatase levels up to 7-fold in the osteoblast-like rat osteosarcoma cell line ROS 17/2.8. This effect was associated with reduced cell growth, and it took place over several days in culture. The increase in enzyme activity was dose dependent (half-maximum .apprx. 1 nM, with a hormone specificity suggesting glucocorticoid receptor mediation). Dexamethasone also increased enzyme activity in ROS 2/3 cells, but not in 2 nonosteoblastic osteosarcoma cell lines; this indicates that, among these cell lines, the effect is specific for osteoblast-like cells. Enzyme activity in both control and dexamethasone-treated cells correlated directly with levels of radioimmunoassayable bone-type isoenzyme. Increases in alkaline phosphatase activity in response to dexamethasone were detectable after .apprx. 5 h, and were inhibited by actinomycin D and cycloheximide. Thus, glucocorticoids appear to increase de novo enzyme synthesis in ROS 17/2.8 cells. The cAMP-elevating agents parathyroid hormone, isoproterenol and 8-bromo-cAMP, which were previously shown to reduce alkaline phosphatase activity in osteoblast-like cells, antagonized the effects of dexamethasone. In the presence of dexamethasone, lower concentrations of these agents were required for inhibitory effects on alkaline phosphatase.