In vitro and ex vivo evidence that estrogens suppress increased bone resorption induced by ovariectomy or PTH stimulation through an effect on osteoclastogenesis.

摘要: The mechanism of bone loss following cessation ovarian function is still unclear. Several studies have shown an increase in turnover natural or surgical menopause which could be prevented by estrogen administration. However, a direct effect on osteoclast-mediated resorption has been difficult to demonstrate vitro. Recent evidence suggested that withdrawal stimulates the production resorbing cytokines, (e.g., interleukin-6, IL-6), regulate osteoclast formation marrow microenvironment. We studied effects 17beta-estradiol osteoclastic resorption, measured as 45calcium release, vitro using cultures fetal mouse long explants different stages development and activity are represented. (10(-12)-10(-8) M) had no basal parathyroid hormone (PTH)-stimulated mature osteoclasts (radii/ulnae) precursors/progenitors (metacarpals) present. 17beta-estradiol, however, inhibited significantly PTH-stimulated osteoclast-free metacarpals cultured together with liver source early progenitors; was also not this system. In ex vivo we further examined culturing cells from ovariectomized (OVX) sham-operated mice release histology. Cocultures OVX increased subsequent compared control cocultures. This either treatment animals for 1 week starting immediately after injection IL-6 neutralizing antibody. conclude estrogens suppress induced PTH through hematopoietic progenitor lineage. Furthermore our data suggest involved OVX.