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Scientists identify a candidate gene for osteoporosis

y 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.

To confirm the involvement of DARC in regulating BMD, Mohan's team characterized the skeletal phenotype of mice with and without the DARC gene. The DARC-knockout mice exhibited increased BMD and lower bone resorption compared to mice with the DARC gene, supporting the predicted role of DARC in hastening bone resorption. They also showed that antibodies to the DARC protein, which effectively blocked the action of DARC, inhibited the formation of osteoclasts.

Although the researchers have identified a number of DNA alterations in the DARC gene, they did not pinpoint the specific alteration that was responsible for the BMD differences between the two strains of mice. However, Mohan and his colleagues predict that changes in the amino acid sequence or alterations in regulatory regions of the DARC gene may lead to key functional changes.

"There are interesting differences between African Americans and Caucasians that could be associated with this gene," explains Mohan. "African Americans exhibit significantly higher BMD compared to Caucasians. Also, African Americans generally do not have the Duffy protein on red blood cells, while Caucasians do. The potential genetic association between DARC gene variation and these traits in humans certainly makes it worthy of further investigation."


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Source:Cold Spring Harbor Laboratory


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