Researchers report the identification of a gene that may play a role in susceptibility to osteoporosis, the crippling disease that leads to bone fractures, especially of the hip and spine.
The study, conducted by scientists at the Musculoskeletal Diseases Center of the Jerry L Pettis Memorial Veteran's Affairs Medical Center at Loma Linda, shows convincing evidence that a gene called DARC negatively regulates bone density in mice. The report appears online in Genome Research .
"If our finding using the mouse model is confirmed in humans, then we may be able to develop therapies that are based on inhibiting the function of the DARC gene," explains Dr. Subburaman Mohan, Ph.D., a Senior Scientist at the Loma Linda VA Medical Center and a Professor of Medicine and Biochemistry at Loma Linda University. "We will also be able to develop genetic screens to identify individuals who are at risk for osteoporosis."
According to the National Osteoporosis Foundation, osteoporosis affects 55% of Americans over the age of 50. Low bone mineral density (BMD), the primary indicator of osteoporosis, is influenced by both genetic and environmental factors (e.g., diet or medication). But the genetic element has been difficult to characterize because bone growth is controlled by many genes, including those for various hormones, growth factors, signaling molecules, and structural components of bone and cartilage.
Previous genetic studies had pointed to a region on mouse chromosome 1 as containing a gene responsible for BMD regulation. In the current project, Mohan and his colleagues honed in on this region of chromosome 1 using a variety of molecular techniques, and they located a gene called DARC (Duffy Antigen Receptor for Chemokines) that exhibited different levels of expression in mice with higher BMD. The analogous chromosomal region has also been shown to influence osteoporosis in humans.
The protein encoded by DARC binds to chemokines or small signaling proteins that are involved in osteoclast formation. Osteoclasts break down bone in a process called bone resorption, releasing important minerals such as calcium, phosphate, and magnesium into the bloodstream. This causes a reduction in BMD.