TAMOXIFEN ATTENUATES GLUCOCORTICOID ACTIONS ON BONE-FORMATION IN-VITRO

Tamoxifen is a synthetic estrogen analog which may regulate osteogenes is in vivo by virtue of its antiglucocorticoid properties. We have exa mined tamoxifen regulation of glucocorticoid-induced osteogenesis in t wo different in vitro bone systems: the chicken periosteal osteogenesi s model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell Line, ROS 17/2.8. I n the CPO model, alkaline phosphatase (AP) activity and collagen synth esis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1 mu M). These Dex-mediated effects were inhibited by increasing concentrat ions of tamoxifen (10-100 mu M). Similarly, in the RBMC model, Dex-dep endent (0.01 mu M Dex) mineralized tissue formation and AP activity we re blocked by tamoxifen (0.1 mu M). Although tamoxifen inhibited Dex-m ediated increases of AP activity in ROS 17/2.8 cells, it did not inhib it uptake of H-3-Dex or of H-3-estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, o steopontin, and osteocalcin. Dex-induced increases for all proteins mR NAs in the RBMC model were not reduced by tamoxifen. Similarly, tamoxi fen had no effects on cellular proliferation. We conclude that tamoxif en has no direct effect on gene expression of bone-related proteins of osteoblastic cells. Further, in the ROS 17/2.8 cell line, the antiglu cocorticoid properties of tamoxifen do not appear to be mediated throu gh either Dex or estrogen receptors.