Scientists identify key mechanism in estrogen's role in preventing bone loss

Scientists have uncovered a significant new link in the chain of immune system events through which estrogen prevents bone loss and that contribute to bone loss when estrogen is deficient. Through research in mice, the scientists discovered that an immune signaling molecule called type b transforming growth factor (TGFb) is responsible for a cascade of events that leads estrogen to prevent bone loss. When TGFb signaling in T cells is blocked, the bone-sparing effects of estrogen are lost. The findings could lead to new therapeutic approaches for preventing bone loss. Results of the research were published online in the Proceedings of the National Academy of Sciences the week of October 25.

The study's senior author was Roberto Pacifici, MD, Herndon professor of medicine and director of the Division of Endocrinology at Emory University School of Medicine. Lead author was Emory research associate Yuhao Gao, PhD.

Previous research has shown that bone loss due to estrogen deficiency is caused by the overexpansion of immune T cells. T cells are known to produce a protein called tumor necrosis factor (TNF), which increases the formation of osteoclasts in rodents and humans. Osteoclasts are cells that help cause the absorption and removal of bone.

In research published in PNAS in August 2003, Dr. Pacifici and his colleagues demonstrated that estrogen deficiency leads to the expression of the immune regulatory protein interferon gamma (IFN-g), which in turn stimulates a protein called class II transactivator (CIITA). They found that increased expression of CIITA leads to expanded antigen presentation by macrophages (immune cells that alert T cells to the presence of invading organisms) and in turn to enhanced T cell activation in the bone marrow and extended T-cell lifespan.

The investigators' new research traces another step in the "upstream" pathway leading to estrogen's effect on bone. In order to model postmenopausal estroge

Contact: Holly Korschun
Emory University Health Sciences Center

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