Chen T L, Cone C M, Feldman D
Endocrinology. 1983 May;112(5):1739-45. doi: 10.1210/endo-112-5-1739.
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.
糖皮质激素是细胞增殖的重要调节因子，但在不同系统中已观察到其作用存在差异。在本研究中，我们检测了糖皮质激素对围产期啮齿动物成骨样细胞原代培养物中细胞增殖的作用。本研究的目的是确定大鼠和小鼠骨细胞对糖皮质激素的反应是否存在种属差异，以及任一物种的反应是否受细胞密度和处理时间的影响。用 dexamethasone 或乙醇载体（小于 0.05%）处理培养的成骨样细胞。通过测量细胞数量、DNA 含量和胸腺嘧啶核苷掺入率来评估增殖率的变化。我们发现，大鼠培养物中对 dexamethasone 的反应取决于处理时的细胞密度：在稀疏培养中起抑制作用，在密集培养中起刺激作用。相比之下，dexamethasone 在所有细胞密度下均抑制小鼠细胞增殖。大鼠细胞中的刺激作用在处理 4 天后出现，但 2 天后未出现。大鼠和小鼠细胞中的刺激和抑制作用均发生在 dexamethasone 浓度为 1.3 - 13 nM 之间，半数最大效应出现在 6 nM 时。发现稀疏和密集大鼠培养物中的不同反应并非源于不同接种密度下细胞亚群的选择性附着。表皮生长因子在两种物种中均具有促有丝分裂作用。在低（1%）或高（10%）血清浓度下，表皮生长因子的存在均未改变 dexamethasone 的作用。总之，这些发现再次强调了种属差异的重要性以及即使在小鼠和大鼠等密切相关物种之间比较一个系统与另一个系统的困难。此外，数据表明处理时的培养条件显著影响这些细胞对糖皮质激素的反应。在研究骨细胞增殖的激素调节时必须考虑这些因素。
