This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The mechanism of increased bone resorption with estrogen is not fully understood, but there is good evidence for effects on osteoclastic precursors of the hematopoietic lineage, and on the osteoblastic cells of mesenchymal lineage that interact with hematopoietic cells to produce osteoclasts. Circulating osteoclast precursors have been clearly demonstrated in peripheral blood, and there is some evidence for circulating osteoblast precursors as well 2. We have shown that short term estrogen treatment can alter the expression of receptor activator of NFligand (RANKL) indicating an effect on the osteoblastic lineage, and the response to macrophage colony stimulating factor (MCSF) and RANKL, indicating an effect on hematopoietic lineage. Initial aim of this study will be to analyze osteoclastogenesis in peripheral blood before and after estrogen treatment, when MCSF, RANKL and other direct stimulators of osteoclastogenesis are added, thus testing the effects on hematopoietic lineage. RANKL expression will also be measured, and if changes are observed, then additional studies to isolate and analyze effects of estrogen on cells of osteoblastic lineage can be carried out.
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