Bone researchers have long known that post-menopausal women are at increased risk of bone loss and diseases such as osteoporosis because of low levels of the hormone estrogen. In recent years, estrogen replacement therapy has been the course of action to prevent bone loss in such women. But not all women are acceptable candidates for this therapy because some may be predisposed to breast, uterine and ovarian cancer risks if they take increased estrogen.

Despite advances in estrogen replacement therapy, it is a source of hot debate in the biomedical community over what cell, molecular and biochemical processes are involved in bone loss associated with declining estrogen levels.

Now a group of biologists at Washington University in St. Louis has shown that lower estrogen levels in post-menopausal women allow a class of inflammatory molecules called cytokines to bind to bone cell surfaces. This in turn gives the green light for specialized cells called osteoclasts to perform their specialty -- bone resorption, or destruction. Moreover, the Washington University team headed by Philip Osdoby, Ph.D., professor of biology in Arts and Sciences, and Teresa Sunyer, Ph.D., research assistant professor of biology, has shown a new relationship between estrogen, bone cell surface receptor proteins and the cytokines Interleukin 1 (IL-1) and Interleukin 8 (IL-8).

Their findings reveal a "cellular espionage" scenario involving signaling receptor proteins and decoy receptor proteins. Osdoby, Sunyer and colleagues found that, in the presence of estrogen, decoy receptor proteins increase in bone cells, preventing cytokines from initiating the path of bone destruction. Without estrogen, signaling receptor proteins flourish and the decoys diminish, letting the osteoclasts erode bone.

The results were published in the May 15, 1999, issue of the Journal of Clinical Investigation. The research was supported by grants from the National Institutes of Health.

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Contact: Tony Fitzpatrick
tony_fitzpatrick@aismail.wustl.edu
314-935-5272
Washington University in St. Louis
26-Jul-1999