Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17 beta-estradiol

In agreement with evidence that estrogens slow the rate of bone remodeling by suppressing the production of both osteoclasts and osteoblasts, loss of estrogens leads to an increase in the number of osteoclast as well as early osteoblast progenitors (CFU-osteoblasts; CFU-OBs) in the murine bone marro w Here we show that CFU-OBs are early transit-amplifying progenitors, i.e., dividing cells capable of limited self-renewal, and that 17 beta -estradio l acts in vivo and in vitro to attenuate their self-renewal by approximatel y 50%. Consistent with a direct receptor-mediated action of estrogens on ea rly mesenchymal cell progenitors, anti-estrogen receptor-alpha (anti-ER alp ha) Ab's stain a small number of marrow cells that exhibit characteristics of primitive undifferentiated cells, including a high nucleus/cytoplasm rat io and lack of lineage-specific biochemical markers; the effect of 17 beta -estradiol on CFU-OB self-renewal is absent in mice lacking ER alpha. Becau se both osteoblasts and the stromal/osteoblastic cells that are required fo r osteoclast development are derived from CFU-OBs, suppression of the self- renewal of this common progenitor may represent a key mechanism of the anti -remodeling effects of estrogens.