PROBING GLUCOCORTICOID-DEPENDENT OSTEOGENESIS IN RAT AND CHICK-CELLS IN-VITRO BY SPECIFIC BLOCKADE OF OSTEOBLASTIC DIFFERENTIATION WITH PROGESTERONE AND RU38486

Glucocorticoids and sex-steroids can modulate osteogenesis in vivo and in vitro. Although the effects of glucocorticoids on bone cells in vi tro have been described in detail, the role of sex-steroids is not as well defined. We examined whether sex-steroids influence bone metaboli sm indirectly by regulating glucocorticoid effects on bone. Interactio ns of the sex-steroid progesterone or its analog RU38486 with the gluc ocorticoid dexamethasone (dex) were studied in functional assays of os teogenesis. Three osteoblastic models were evaluated: (1) the rat bone marrow stromal cell (RBMC) nodule system; (2) the chick periosteal os teogenesis (CPO) model; and (3) ROS 17/2.8 cells. RU38486, progesteron e, and unlabelled dex competitively inhibited H-3-dex uptake by ROS 17 /2.8 cells as well as its (H-3-dex) binding to cytosol preps. Both RU3 8486 and progesterone inhibited dex-induced increases in alkaline phos phatase in CPO cultures, in RBMC cultures, and in ROS 17/2.8 cells. De x-induced decreases in cell proliferation in ROS 17/2.8 cells were rev ersed by RU38486 but dex-induced increases in proliferation in the CPO model were not affected. In CPO cultures, dex-induced increases in co llagen synthesis were inhibited completely by RU38486 and progesterone . Dex-dependent nodule formation in the RBMC was blocked by RU38486. B oth RU38486 and dex mediated reduction of calcium uptake in the CPO mo del but did not affect mineralized tissue area. The data indicate that RU38486 and progesterone competitively inhibit dex-mediated stimulati on of osteogenesis in vitro; this inhibition is exerted on early but n ot late stage differentiation events of osteoprogenitor cells. (C) 199 5 Wiley-Liss, Inc.