Novel Protein Technology Triggers Rapid Bone Growth

A protein involved in tissue growth in animals such as salamanders, zebrafish, and mice can also stimulate the regeneration of damaged human bone, according to a new study.

Researchers at the Stanford University School of Medicine (CT, USA) stimulated the rapid bone growth in laboratory mice by injecting them with a protein called Wnt, packaged in a form that could be used in humans, opening the door to additional experiments to heal skin, muscle, brain, and other tissue injuries. It may also eventually provide a much-needed alternative to currently available drugs based on bone morphogenetic proteins (BMPs), which are approved for use in humans to speed bone growth in spinal fusions and long bone fractures, but have become increasingly associated with a number of adverse side effects.

Wnt, a key player in tissue regeneration in many organisms, was exceedingly difficult to purify in an active form and, once isolated, was found to be both insoluble and hydrophobic. The researchers at Stanford succeeded in overcoming this problem by using liposomes--tiny, hydrophilic molecular bubbles. The researchers planted laboratory-made Wnt on the liposomes bubble's outer surface, thus allowing it to be suspended in liquid for delivery into the body. To test the delivery method, the researchers drilled one-millimeter holes into the leg bones of the mice with a high-speed dental drill. They then injected the Wnt-covered liposomes at the site of the damage and compared the rate and pattern of bone formation with that of control animals, and with that of animals injected with Wnt without a liposomal escort.

The researchers found that within three days, the animals who had received Wnt had 3.5 times more new bone than the other two groups; and after 28 days, the newly formed bone had completely healed, while the control animals were still in the process of repairing the injury.
Further investigation showed that Wnt works by increasing the proliferation of bone progenitor cells, which then became new bone, mimicking the way Wnt-activated healing occurs naturally. Laboratory mice that had been genetically modified to have a more prolonged Wnt signal also healed more quickly than did control mice, and as in other animals, the Wnt pathway was found to be activated in response to injury and required for normal healing. The study was published in the April 28, 2010, online issue of the journal Science Translational Medicine.

"We believe our strategy has the therapeutic potential to accelerate and improve tissue healing in a variety of contexts,” said lead author professor of surgery Jill Helms, D.D.S., Ph.D. "After stroke and heart attack we heal the injuries slowly and imperfectly, and the resulting scar tissue lacks functionality. Using Wnt may one day allow us to regenerate tissue without scarring.”

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Insights into the mechanisms of Wnt action have emerged from several systems: genetics in Drosophila and Caenorhabditis elegans, ectopic gene expression in Xenopus embryos, and biochemistry in cell cultures. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling.

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Stanford University School of Medicine