Fig. 4.

Proposed model of the osteoclastic ERα-mediated osteoprotective action of estrogens through attenuation of bone resorption by inducing osteoclastic cell death. Estrogens (17β-estradiol) activate ERs in functionally opposing types of bone cells: osteoblasts, which derive from mesenchymal stem cells, and osteoclasts, multinucleated giant cells derived from hematopoietic stem cells. The estrogen-dependent induction of FasL gene expression in these bone cells triggers apoptosis in mature osteoclasts.