Gene Promotes Bone Formation

In the United States alone, approximately 54 million people older than age 50 years suffer from osteoporosis and aging-related bone loss, and the number of cases is expected to balloon to 64.4 million by 2030. Studies suggest that worldwide, one in 3 women and one in 5 men older than 50 will experience osteoporosis-related bone fractures. Osteporosis is caused when the process of bone resorption overpowers the process of bone formation. Bone loss is further exacerbated by chronic inflammation, often associated with aging. Most current osteoporosis medications are developed to slow bone loss by targeting the resorption. Researchers have taken an important step toward a more effective treatment of osteoporosis. Led by Dr. Cun-Yu Wang of the University of California, Los Angeles (UCLA) School of Dentistry, researchers are developing a novel therapeutic agent that not only slows down bone destruction, but also promotes bone formation by suppressing inflammation in the bone marrow. The team discovered that a growth factor called Wnt4 that is secreted into the bone marrow effectively prevents bone loss in mouse models of osteoporosis and skeletal aging. It does this by inhibiting NF-кB signaling, a key pathway in the body’s inflammatory processes. Wang’s team previously found that Wnt4 protein could promote bone formation; in the new study, they created a strain of transgenic mice in which the Wnt4 gene was overexpressed in osteoblasts, or bone-forming cells. As expected, those mice exhibited increased bone mass compared with the control group, and they showed significantly less bone loss in an osteoporosis model. The team discovered that Wnt4 protein both promotes osteoblasts and suppresses the activity of osteoclasts, or bone-resorbing cells, as well as inflammation in the bone marrow. This research supports the theory that recombinant Wnt4 protein could potentially be useful for treatment of osteoporosis and aging-related bone loss.
(Source: UCLA School of Dentistry, August 11, 2014)


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