Comparative effects of estrogen and antiestrogens on differentiation of osteoblasts in mouse bone marrow culture

Estrogens as well as some antiestrogens have been shown to prevent bone los s in postmenopausal women. These compounds seem to inhibit bone resorption, but their anabolic effects have been less explored. In this study, bone ma rrow cultures were used to compare the effect of 17 beta-estradiol (E2), an d two triphenylethylene derivatives, tamoxifen (TAM), and FC1271a, and a be nzothiophene derivative raloxifene (RAL) on differentiation of osteoblasts. AII enhanced osteoblastic differentiation of 21-day cultures as indicated by increased mineralization and bone nodule formation. All, except RAL, sti mulated cell proliferation during the first 6 days of the culture. However, in the presence of RAL the content of total protein was increased in 13-da y cultures. SDS-PACE and autoradiography of [C-14]-proline labeled proteins revealed elevated level of the newly synthesized collagen type I. The pure antiestrogen ICI 182,780 abolished the increase of the specific activity o f alkaline phosphatase by E2, TAM, and FC1271a but not the effect of RAL on protein synthesis. Our results show that E2 as well as TAM, FC1271a, and R AL stimulate bone formation in vitro but the mechanism of the anabolic acti on of RAL in bone clearly differs from that of E2, TAM, and FC1271a. (C) 19 99 Wiley-Liss, Inc.