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"This was not what we were trying to do in the lab. But what we've found could become an amazing way to jump-start local bone formation," says Janet Rubin. (Credit: University of Liverpool Faculty of Health & Life Sciences/Flickr)

bones

Awesome ‘accident’ turns stem cells into bone

Medical researchers were surprised when they discovered a new way to turn stem cells into bone cells—and ultimately trigger bone growth in mice.

The team expected the stem cells to become fat cells.

“This was not what we expected. This was not what we were trying to do in the lab. But what we’ve found could become an amazing way to jump-start local bone formation,” says Janet Rubin, a professor of medicine at the UNC School of Medicine.

actin fibers
Left: Green actin fibers create architecture of the cell. Right: With cytochalasin D added, actin fibers disband and reform in the nuclei. (Credit: UNC School of Medicine)

Rubin and colleagues used cytochalasin D, a naturally occurring substance found in mold, as a proxy to alter gene expression in the nuclei of mesenchymal stem cells to force them to become osteoblasts (bone cells).

By treating stem cells—which can become fat or bone cells—with cytochalasin D the result was clear: The stem cells became bone cells. Further, injecting a small amount of cytochalasin D into the bone marrow space of mice caused bone to form. This research, published in the journal Stem Cells, details how the scientists altered the stem cells and triggered bone growth.

“And the bone forms quickly,” says Rubin, the paper’s senior author. “The data and images are so clear; you don’t have to be a bone biologist to see what cytochalasin D does in one week in a mouse.”

At the center of the discovery is a protein called actin, which forms fibers that span the cytoplasm of cells to create the cell’s cytoskeleton. Osteoblasts have more cytoskeleton than do adipocytes (fat cells).

‘It goes against everything in the literature’

Buer Sen, the paper’s first author and research associate in Rubin’s lab, used cytochalasin D to break up the actin cytoskeleton. In theory—and according to the literature—this should have destroyed the cell’s ability to become bone cells. The cells, in turn, should have been more likely to turn into adipocytes.

Instead, Sen found that actin was trafficked into the nuclei of the stem cells, where it had the surprising effect of inducing the cells to become osteoblasts.


When cytochalasin D is added to mesenchymal stem cells (right), the protein fibers made of actin are wreaked but reform inside the nuclei, where they kick start the process to turn the stem cells into bone cells.

“My first reaction was, ‘No way, Buer,'” Rubin says. “‘This must be wrong. It goes against everything in the literature.’ But he said, ‘I’ve rerun the experiments. This is what happens.'”

[Scientists grow ‘mini kidneys’ in petri dishes]

Rubin’s team expanded the experiments while exploring the role of actin. They found that when actin enters and stays in the nucleus, it enhances gene expression in a way that causes the cell to become an osteoblast.

“Amazingly, we found that the actin forms an architecture inside the nucleus and turns on the bone-making genetic program,” Rubin says. “If we destroy the cytoskeleton but do not allow the actin to enter the nucleus, the little bits of actin just sit in the cytoplasm, and the stem cells do not become bone cells.”

Rubin’s team then turned to a mouse model. Using live mice, they showed that cytochalasin D induced bone formation in mice.

Bone formation in mice isn’t very different from that in humans, so this research might be translatable. And while cytochalasin D might not be the actual agent scientists use to trigger bone formation in the clinic, Rubin’s study shows that triggering actin transport into the nuclei of cells may be a good way to force mesenchymal stem cells to become bone cells.

The National Institutes of Health funded the research.

Source: UNC-Chapel Hill

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