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Research Interests
Allison K. Wilson, Ph.D.
Professor of Biology
Osteoporosis is an increasing concern as the baby boomer population ages. It is important to better understand the mechanism by which environmental estrogens such as cadmium exert their effects on bone to be able to develop new strategies by which to address these toxicants and lead to new treatments for osteoporosis.
The overall objective of my research program is to determine mechanisms by which cadmium causes bone loss. Animal models indicate that bone loss responses occur at blood cadmium concentrations in the range of levels reported for persons who smoke cigarettes and for workers with low-level cadmium exposure in industry. Cadmium-induced bone loss is also more pronounced in animals that have experienced increased bone stress, such as during estrogen deficiency, suggesting that women exposed to cadmium are at increased risk for postmenopausal osteoporosis. Osteoclasts, the bone resorbing cells, appear to be more sensitive to low, environmentally-relevant levels of cadmium in organ and cell culture systems than osteoblasts, the bone forming cells. For this reason, my research is focused on the osteoclast.
Increased bone resorption can be a result of the formation of increased numbers of osteoclasts from progenitors and/or precursors. In addition, resident, inactive osteoclasts can be immediately upregulated to increase bone resorption by either increasing the number of osteoclasts activated and/or by increasing the activity of a few osteoclasts to a greater extent. Cadmium has been demonstrated to shorten the timecourse of osteoclast differentiation, promote the fusion of osteoclast precursors, increase the bone resorbing activity of osteoclasts and lengthen the lifespan of the osteoclast by delaying the onset of estrogen-induced apoptosis. The primary focus of my research program is to investigate the signaling pathways for delaying induced osteoclast apoptosis in response to cadmium exposure, thus allowing osteoclasts more time to resorb bone.
Apoptosis is induced in differentiated osteoclasts from primary spleen cultures and a preosteoclastic cell line to 1) investigate the nongenomic/indirect genomic pathways of cadmium action on induced-osteoclast apoptosis and 2) determine whether the antiestrogenic effect on induced-osteoclast apoptosis is specific to low-level cadmium exposure or is a general metal effect.
An additional research interest is to determine the role of CYR61 protein in the cadmium response on bone. CYR61 has been identified through microarray analysis to be an early message induced by cadmium. Experiments are underway to establish whether cadmium induces CYR61 protein expression in osteoclasts and/or osteoblasts. Since CYR61 is an activator of integrins essential for osteoclast function, we are investigating the effects of inhibiting CYR61 expression on bone cell function.
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