Researchers at the University at Buffalo have described a novel pathway by which estradiol, the primary estrogen in humans, aids in maintaining bone density, a function critical to avoiding osteoporosis.
It is well known that estrogen is essential for healthy bone, and that when the production of estrogen is reduced, as occurs normally in postmenopausal women and pathogenically after exposure to radiation or chemotherapeutic drugs, bones become brittle and break easily. However, the mechanisms involved aren't clearly understood.
The new study found that one way estradiol helps to maintain bone density is by stopping the activation of an enzyme known as caspase-3. Also called the executioner caspase, caspase-3 is the central player in initiating the process of apoptosis, or programmed cell death of osteoblasts, the bone cells that aid in the growth and development of new bone and teeth.
Peter G. Bradford, Ph.D., senior author on the study said of the results: "Basic and clinical studies have shown that estrogens can prevent both bone loss and reduce the incidence of bone fractures. Our research at the molecular and cellular level suggests that the underlying basis of this protective effect of estrogens involves the prevention of apoptosis in osteoblasts and that the key event in this prevention is the inhibition of caspase-3 activity."
Bradford is an associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences and associate professor of oral biology in the UB School of Dental Medicine. Kenneth V. Gerace, a third-year dental student in his laboratory, is first author on the study.
To determine the effect of estradiol on caspase-3 activity, one group of human osteoblasts was treated with estradiol for 24 hours and another group was not. Both groups then were exposed for 24 hours to a drug called etoposide, a cancer chemotherapeutic drug that promotes apoptosis.