Principal Investigator: Gerard P. Ahern, PhD
Osteoporosis is a leading cause of bone fracture, particularly in women; about half of women over 50 will fracture the hip, wrist or vertebra. Estrogen-deprivation promotes bone loss and current treatments revolve around estrogen or bisphosphonates, but none is ideal.
As the nation’s 72 million baby boomers age, the burden of bone disorders will increase significantly, making better prevention and treatment strategies more urgent.
A common feature of menopause is enhanced bone inflammation. GUMC’s Gerard Ahern, Ph.D., associate professor of pharmacology and physiology, and his research team postulate that inflammation detecting proteins may be important drivers of bone loss. A major inflammation receptor, called “wasabi” receptor or TRPA1, is located in bone-forming cells and in nearby sensory nerves.
To explore a prevention or treatment role for TRPA1 in osteoporosis, the team examined bone loss in mice following removal of their ovaries (to mimic estrogen loss). Notably, they found that while estrogen deprivation causes a marked decrease in bone density in normal mice, mice engineered to lack TRPA1 show minimal or no bone loss. They hypothesize that TRPA1 plays a critical role in osteoporosis and may represent a useful target for drug therapy.
An important step in developing a TRPA1 drug is to determine the precise location of bone density controlling TRPA1. Ahern and his team’s first goal is to measure the effects of estrogen-deprivation in mice with TRPA1 protein deleted from bone cells or sensory nerves. The results will determine whether the cell or nerve site is critical for the effects of TRPA1 on bone, information useful in developing drugs to target TRPA1 in discrete tissues with potentially fewer side effects.
The research scientists’ second goal is to further explore the utility of TRPA1 as a drug target by measuring the effects of strontium on bone cells and neurons. Strontium, like its metal counterpart calcium, has positive effects on bone formation. In Europe, a highly absorbable form of strontium, strontium ranelate, already is available as a prescription drug to treat severe osteoporosis.
Ahern’s lab recently showed that strontium inhibits the TRPA1 protein. They plan to test whether strontium produces positive effects on bone-forming cells by blocking TRPA1. These experiments will validate TRPA1 as a therapeutic agent for osteoporosis or remove it from contention.