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Researchers On The Path To Building Bone

UAB (University of Alabama at Birmingham) researchers have developed a method to increase bone density in mice, a development that might have future benefit for humans in// the treatment of osteoporosis and bone fracture. The research, published in the Jan. 29 issue of Proceedings of the National Academy of Sciences, involves manipulation of the Pten gene, which contributes to the process by which cells die, known as apoptosis.

“Bone density can increase either because more bone cells divide or fewer cells die due to apoptosis. Pten is a tumor suppressor gene that applies a break on the main cell survival pathway, causing cells to die,” said Thomas L. Clemens, Ph.D., professor of pathology and director of the UAB Division of Molecular and Cellular Pathology. “We devised a way to remove the Pten break in bone cells, allowing the cells to stay alive and active for a longer period of time.”

Clemens, a scientist in the UAB Center for Metabolic Bone Disease, and his colleagues disrupted Pten in bone cells called osteoblasts in mice. The mice with Pten disruption, while normal sized, had dramatic and progressively increasing bone density throughout life compared to controls.

“In the mice without Pten, osteoblast cells survived longer and continued to make new bone long after they ordinarily would have died,” Clemens said. “This increased osteoblast production led to greater bone density. If we can translate these findings to human conditions such as osteoporosis or bone fracture, we can potentially not only prevent bone loss, but actually increase bone density in humans as they age.”

Humans lose bone as they age, in part because of the loss of osteoblast cells that have died, leading to conditions such as osteoporosis or its predecessor, osteopenia.

While there are medications available to treat these conditions by slowing bone loss, there are no agents that contribute to building new bone and increasing bone de nsity after it has already been lost.

Clemens stresses that this research is in the very early stages and it could be years before treatments for human conditions would be possible.

“The key will be to find a way to selectively turn off Pten only in bone-making osteoblasts and leave other cells in the body unaffected,” Clemens said. “Pten plays an important role in the body by killing cell lines that are proliferating out of control, as in tumors.”

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