Stanford researchers found that activating bone stem cells helps repair fractures in diabetic mice. Applying a protein to the fracture site increased the expression of key signaling proteins and enhanced healing in the animals. Bone fractures in diabetic mice heal better in the presence of a protein that stimulates the activity of skeletal stem cells, according to a study by researchers at the Stanford University School of Medicine.

The protein counteracts a decrease in stem cell activity that the researchers observed both in mouse models of diabetes and in bone samples from diabetic patients who had undergone joint replacements. The researchers hope the discovery will lead to ways to help people with diabetes heal more efficiently from broken bones.

“We’ve uncovered the reason why some patients with diabetes don’t heal well from fractures, and we’ve come up with a solution that can be locally applied during surgery to repair the break,” said Michael Longaker, MD, co–director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.

The study was published Jan. 11 in the journal Science Translational Medicine. Longaker, a professor of plastic and reconstructive surgery, shares senior authorship of the study with Charles Chan, PhD, an instructor at the stem cell institute. Postdoctoral scholar Ruth Tevlin, MD, is the lead author.

The researchers used a mouse model of Type 2 diabetes, in which the disease arises when the animals are about 4 weeks old. Prior to the development of the disease, the prediabetic mice were able to heal leg bone fractures as effectively as wild–type mice, the researchers found. In contrast, after the disease had manifested itself, the repaired bone was significantly weaker and less dense than the bone in the control animals. When they compared the numbers of skeletal stem cells (SSCs) in the healing bone seven days after fracture, they found that the diabetic mice had significantly lower numbers of these cells than did the control animals.

When Tevlin and her colleagues analyzed that environment, they found that the diabetic animals produced significantly lower levels of a family of signaling proteins, called hedgehog, that is known to play a critical role in many biological processes, including embryonic development and tissue regeneration.