INHIBITION OF BONE-RESORPTION BY 17-BETA-ESTRADIOL IN HUMAN BONE-MARROW CULTURES

Estrogen deficiency puts individuals at risk of developing osteoporosi s because it causes increased bone resorption. However, the mechanism by which this occurs is not known. We have shown, using a recently des cribed two-phase human bone marrow culture system, that estradiol (17 beta-E-2) added to phase I results in inhibition of bone resorption by reducing the number of osteoclasts (identified as vitronectin recepto r and/or calcitonin receptor-positive cells) formed in the cultures. T he addition of 17 beta-E-2 in phase II was without effect, indicating that it does not interfere with the bone resorptive process. 17 beta-E -2 down-regulated mRNA expression and protein synthesis of the membran e form of macrophage colony-stimulating factor (M-CSF). 17 beta-E-2 di d not the alter the expression of the 4.0 kb M-CSF transcript. However , it increased protein synthesis of the proteoglycan form of M-CSF, bu t not the 85 kDa soluble form in the same cultures. Finally, addition of M-CSF to the cultures reversed the 17 beta-E-2-induced inhibitory e ffect. These observations suggest that regulation of the synthesis of membrane-bound M-CSF plays a role in 17 beta-E-2-induced inhibition of bone resorption. (C) 1998 Wiley-Liss, Inc.