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Mouse studies reveal immune mechanism involved in bone loss caused by estrogen deficiency

ATLANTA- Scientists have uncovered in mice a key mechanism of the immune system involved in the bone loss that results from estrogen deficiency. If confirmed in human studies, the findings would demonstrate that postmenopausal osteoporosis is the result of an inappropriate immune response triggered by estrogen deficiency. The research also could help explain why estrogen deficiency appears to exacerbate autoimmune diseases, such as rheumatoid arthritis.

Results of the research will be published in the online edition of the Proceedings of the National Academy of Sciences the week of August 4. The study's senior author was Roberto Pacifici, MD, professor of medicine and director of the Division of Endocrinology at Emory University School of Medicine. Lead author was Simone Cenci, MD, now at the San Raffaele Scientific Institute in Milan, Italy. Other authors included Gianluca Toraldo and Oscar Sierra from Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, and M. Neale Weitzman, Cristiana Roggia and Wei Ping Qian from Emory School of Medicine.

Scientists already had discovered that bone loss caused by estrogen deficiency results from the overexpansion of T cells in the immune system. Immune T cells are known to produce a protein called tumor necrosis factor (TNF) that increases the formation of osteoclasts in rodents and humans cells that help cause the absorption and removal of bone. T cell proliferation is typically caused by the activation of T cells, but until now scientists have not understood exactly why and how estrogen deficiency causes the T cells to become activated. In order to model postmenopausal estrogen deficiency, the scientists removed the ovaries from mice, then studied the mouse T cells in culture. They confirmed that T cell activation was jump started by the immune regulatory protein interferon gamma (IFN-g), which in turn stimulated a protein called class II transactivator (CIITA). They foun
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
4-Aug-2003


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