Glucocorticoid modulation of cell proliferation in cultured osteoblast-like bone cells: differences between rat and mouse.

Abstract

Glucocorticoids are important regulators of cell proliferation, but divergent effects have been noted in various systems. In this study, the actions of glucocorticoids on cell proliferation were examined in primary cultures of osteoblast-like cells from perinatal rodents. The aim of the study was to determine whether rat and mouse bone cells exhibit species differences in their responses to glucocorticoids and whether the response of either species was influenced by the cell density and time of treatment. Cultured osteoblast-like cells were treated with dexamethasone or ethanol vehicle (less than 0.05%). Changes in the proliferation rate were assessed by measurement of cell number, DNA content, and thymidine incorporation rate. We found that the response to dexamethasone was dependent on the cell density at the time of treatment in rat cultures: inhibitory in sparse and stimulatory in dense cultures. In contrast, dexamethasone inhibited mouse cell proliferation at all cell densities. The stimulatory effects in rat cells were seen after 4 days of treatment but not after 2 days. Both the stimulatory and inhibitory effects in rat and mouse cells occurred between dexamethasone concentrations of 1.3-13 nM, with half-maximal effects seen at 6 nM. The divergent responses in sparse and dense rat cultures were found not to result from the selective attachment of cell subpopulations at different plating densities. Epidermal growth factor was mitogenic in both species. The effects of dexamethasone were not modified by the presence of epidermal growth factor in either low (1%) or high (10%) serum concentrations. In conclusion, these findings reemphasize the importance of species differences and the difficulty in comparing one system to another, even with closely related species such as mouse and rat. Furthermore, the data show that the culture conditions at the time of treatment dramatically influence the responses of these cells to glucocorticoids. These factors must be considered in studies of the hormonal regulation of bone cell proliferation.