Effect of retinoids on the growth, ultrastructure, and cytoskeletal structures of malignant rat osteoblasts

A clonal rat osteogenic sarcoma cell line, UMR 106-06, was used to study the effects of retinoic acid (RA) on its growth and morphology. Retinoic acid caused a reversible, time and dose-dependent inhibition of growth. RA-treated cells were larger, were more adherent to the substratum, and contained fewer mitotic figures. Half-maximal growth inhibition was observed at 10(-8) M. Among the naturally occurring retinoids, RA was clearly the most potent while the arotinoids, Ro 13-7410 and Ro 13-6298, were approximately 50 times more potent than was RA. A similar range of potencies was observed in the cloning efficiencies of the cells in soft agar. Fluorescence microscopy revealed that RA treatment increased the cellular content and organization of F-actin fibers. Ultrastructural changes include decreased chromatin dispersion and increased number of nucleoli per nucleus, decreased rough endoplasmic reticulum, decreased electron density and number of mitochondria, and increased formation of microfilaments and microtubules. These results identify this clonal cell line, which has been extensively characterized as the malignant counterpart of the normal osteoblast, as a target for vitamin A action.