The effects of sodium butyrate on the retinoic acid-induced changes in 1,25-dihydroxyvitamin D3 receptors in tumorigenic and nontumorigenic bone derived cell lines.

Retinoic acid has previously been shown to alter 1-25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in tumorigenic (ROS 17/2A, UMR 106M) and nontumorigenic (RCJ 1.20) bone-derived cells. The mechanism of this regulation is unclear. In the present series of experiments, we have investigated the mechanism of the retinoic acid-induced increase in 1,25-(OH)2D3 receptors by studying the effects of sodium butyrate on this process. In ROS 17/2A rat osteosarcoma cells, retinoic acid induced a 2-4-fold increase in 1,25-(OH)2D3 receptors in proliferating cells but only a 1.5- to 2-fold increase in nonproliferating cells. The retinoic acid-induced increase in 1,25-(OH)2D3 receptors in proliferating ROS 17/2A cells was inhibited by sodium butyrate, but sodium butyrate had no effect on the retinoic acid-induced increase in 1,25-(OH)2D3 receptors in nonproliferating cells. Pretreatment with hydroxyurea of low density cells decreased the effect of retinoic acid, and abolished the sodium butyrate inhibition, indicating that the differing effects of retinoic acid in high and low density cells are related to cell proliferation and not to cell density or time of exposure to retinoic acid. In low density UMR 106M cells, the effects of retinoic acid and sodium butyrate on the number of 1,25-(OH)2D3 receptors were similar to those in ROS 17/2A cells. However, in RCJ 1.20 cells, a nontumorigenic cell line with some of the characteristics normally attributed to osteoblasts, the effects of retinoic acid and sodium butyrate were opposite: retinoic acid caused a decrease in the number of 1,25-(OH)2D3 receptors, which was inhibited by sodium butyrate. The possibility that the different responses observed between the two osteosarcoma cell lines and the RCJ 1.20 cells constitute differences in response pattern between tumorigenic and nontumorigenic cell lines is of interest, but requires further experimentation to verify.