Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips
Imagine you have a bone fracture or a hip replacement, and you need bone to form, but you heal slowly - a common fact of life for older people. Instead of forming bone, you could form fat. Researchers at the University of North Carolina School of Medicine may have found a way to tip the scale in favor of bone formation. They 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," said Janet Rubin, MD, senior author of the paper and professor of medicine at the UNC School of Medicine. "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."
Rubin added, "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. However, this will not address osteoporosis, which involves bone loss throughout the skeleton."
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). Buer Sen, MD, first author of the Stem Cells paper 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.
"My first reaction was, 'No way, Buer,'" Rubin said. "'This must be wrong. It goes against everything in the literature.' But he said, 'I've rerun the experiments. This is what happens.'" 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 said. "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.
Rubin, the vice chair for research at the UNC School of Medicine, holds join appointments in pediatrics and pharmacology, and is an adjunct professor of bioengineering.
This work was funded by the National Institutes of Health.
Mark Derewicz | EurekAlert!
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences