BioEd Online

Proteins that are known to boost the growth of the skeleton have now been used to heal broken bones in mice — with the help of tiny capsules that shuttle the healing protein to the site of injury.

Roel Nusse and his colleagues at Stanford School of Medicine in Palo Alto, California, found that injecting mice with a family of proteins called Wnts — packed inside lipid bubbles, or liposomes — triggers new bone growth within a few days. They report their findings today in Science Translational Medicine¹.

Wnt proteins are known to stimulate bone formation and tissue regeneration, but scientists have not managed to turn them into drugs because the proteins are not very stable, and they tend to clump together instead of migrating to injuries. Inspired by methods used to deliver drugs to tumours, Nusse and his colleagues previously found in 2008 that encasing purified Wnt proteins inside liposomes enhances the activity of the proteins in healthy mice². Now they have tested the protein-delivery system in injured animals for the first time.

"It's a major technological advance, and the fact that Wnts promote bone regeneration is an important finding," says Gerard Karsenty, an expert in skeleton physiology at Columbia University in New York City. "They used a very clever way of delivering Wnts."

Speed healing

Nusse and his team inactivated a gene in mice called Axin2, which usually dampens Wnt signalling. By inactivating this gene, they created a prolonged, amplified Wnt signal in the mice and found that immature bone cells started to mature faster than in normal mice. When they drilled tiny holes into the leg bones of these mice lacking Axin2, they noticed that cells in injured areas multiplied and matured more quickly than cells in intact tissue or in normal mice. As a result, bones in these mice started to regrow within a few days — faster than broken bones in normal mice, which can take several weeks to heal.

The team next injected the injured mice with the Wnt capsules and found that bones started to regrow within a few days, and the skeletal defects healed faster than mice injected with empty vesicles alone.

Wnt proteins may have an edge over another family of healing proteins called bone morphogenetic proteins (BMPs), which have been used to treat skeletal injuries in humans but can cause bone tissue to grow in the wrong place. "Whether the new approach is better than BMPs, I don't know," Karsenty says. "But it is certainly promising."

Because Wnt proteins can repair a range of tissues, Nusse says that the technique might be able to treat not only fractures and osteoporosis, but also diseases of the skin, heart and brain. The researchers have applied for a patent for the therapeutic use of their Wnt delivery system, and they plan on testing the method in different tissues. Future experiments may also reveal which cells prompt healing in response to the Wnt proteins, and allow the researchers to compare how well BMPs and Wnts treat different types of injury.

Before starting clinical trials, the team will first have to determine whether the Wnt therapy is safe at high doses and over prolonged periods of time. Humans and mice share a similar Wnt pathway, Nusse says. "It's not unlikely that it would work in humans," he says. "But I don't know how dramatic the effect is going to be."