Conditioned medium of estrogen-treated osteoblasts inhibits osteoclast maturation and function in vitro

The increase of bone resorption and reduction of bone mass in postmenopausa l women can be prevented by treatment with estrogen, Although it is well es tablished that estrogen treatment normalizes the increased bone turnover, t he mechanism by which estrogen exerts its protective influence at the cellu lar and molecular level in bone remains elusive. It has been shown that ost eoblasts are involved in osteoclast development and osteoclastic bone resor ption, In this work we examine the effect of estrogen (E-2) on osteoclast-m ediated bone resorption via the medium conditioned by osteoblast cultures. The conditioned medium collected from osteoblast cultures without (CM) or w ith 0.1 nmol/L 17 beta-estradiol (E-CM) was mixed in a 1:1 ratio with fresh osteoclast culture medium. Osteoclasts were isolated from the bone marrow of 3-day-old NMRI mice and cultured on bovine bone slices. The total number of multinucleated tartrate-resistant alkaline phosphatase (TRAP)-positive cells in cultures with CM and E-CM was similar to that of cells incubated i n control medium, However, the number of osteoclasts containing more than t hree nuclei was significantly smaller in the cultures containing E-CM, The total area of resorption was only slightly decreased in cultures containing CM, but was markedly inhibited in cultures with E-CM, In osteoblast cultur es, the production of interleukin (IL)-1 and IL-6, but not of TNF-alpha, wa s reduced by 0.1 nmol/L E-2, Our data suggest that E-2 treatment of osteobl asts decreases the production of factor(s) that induces osteoclast differen tiation to multinucleated cells with a higher capacity for bone resorption, (C) 1999 by Elsevier Science Inc. All rights reserved.