Unlocking a key behind why our bones get weaker as we age

Magnified image of a bone with osteoporosis. Photo Courtesy Sciencephoto.com

Getting older brings with it a mixed bag of items. If you are lucky you can get wiser. If you are not so lucky you can get osteoporosis. But while scientists don’t know how to make you wiser, they have gained some new insights into what makes bones weak and so they might be able to help with the osteoporosis.

Around 200 million people worldwide suffer from osteoporosis, a disease that causes bones to become so brittle that in extreme cases even coughing can lead to a fracture.

Scientists have known for some time that the cells that form the building blocks of our skeletons are found in the bone marrow. They are called mesenchymal stem cells (MSCs) and they have the ability to turn into a number of different kinds of cells, including bone or fat. The keys to deciding which direction the MSCs take are things called epigenetic factors, these basically control which genes are switched on or off and in what order. Now researchers from the UCLA School of Dentistry have identified an enzyme that plays a critical role in that process.

The team found that when the enzyme KDM4B is missing in MSCs those cells are more likely to become fat cells rather than bone cells. Over time that leads to weaker bones and more fractures.

In a news release Dr. Cun-Yu Wang, the lead researcher, said: “We know that bone loss comes with age, but the mechanisms behind extreme cases such as osteoporosis have, up until recently, been very vague.”

To see if they were on the right track the team created a mouse model that lacked KDM4B. Just as they predicted the MSCs in the mouse created more fat than bone, leading to weaker skeletons.

They also looked at mice who were placed on a high fat diet – something known to increase bone loss and weaker bones in people – and found that the diet seemed to reduce KDM4B which in turn produced weaker bones.

In the news release Dr. Paul Krebsbach, Dean of the UCLA School of Dentistry, said the implications for the research are enormous. “The work of Dr. Wang, his lab members and collaborators provides new molecular insight into the changes associated with skeletal aging. These findings are an important step towards what may lead to more effective treatment for the millions of people who suffer from bone loss and osteoporosis.”

The study is published in the journal Cell Stem Cell.

New hydrogel developed could aid in therapies to generate bones in head and neck

Taking a cue from mussels’ natural ability to adhere to surfaces underwater, the UCLA researchers incorporated an alginate-based solution in their hydrogel.
Photo taken by D. Jude, Univ. of Michigan

When most people think of mussels, what immediately comes to mind might be a savory seafood dish or favorite seafood restaurant. But to Dr. Alireza Moshaverinia and his team of researchers at the UCLA School of Dentistry, it’s the ability that mussels have to stick to wet surfaces that is of particular interest.

Partially inspired by this concept and with support from CIRM, the team of researchers developed the first adhesive hydrogel specifically to regenerate bone and tissue defects following head and neck injuries.

Over the past few years, surgeons and clinicians have began to use hydrogels to administer stem cells to help regenerate lost tissues and for bone defects. Hydrogels are beneficial because they can be effective at carrying stem cells to targeted areas inside the body. However, when used in surgeries of the mouth, they tend to become less effective because blood and saliva prevent them from properly adhering to the targeted site. As a result of this, the stem cells don’t stay in place long enough to deliver their regenerative properties.

To help with this problem, the researchers at UCLA developed a new hydrogel by adding alginate into the mix. Alginates are found in the cells of algae and form a sticky, gum-like substance when wet.

The scientists then tested their new hydrogel by loading it with bone building stem cells and applying it to the mouths of rats with an infectious disease that affects the bone structure. They then sealed the hydrogel in place and applied a light treatment, similar to what dentists use in humans to solidify dental fillings.

The results showed that the bone around the implants in all of the rats had completely regenerated.

In a news release from UCLA, Dr. Moshaverinia elaborates on what this study means for potential future treatments.

“The light treatment helped harden the hydrogel, providing a more stable vehicle for delivery of the stem cells. We believe that our new tissue engineering application could be an optimal option for patients who have lost their hard and soft craniofacial tissues due to trauma, infection or tumors.”

The full study was published in Science Translational Medicine.