Research ArticleBone

Wnt Proteins Promote Bone Regeneration

Science Translational Medicine  28 Apr 2010:
Vol. 2, Issue 29, pp. 29ra30
DOI: 10.1126/scitranslmed.3000231

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Editor's Summary

Some of the best medicines act as facilitators. They tweak the body’s systems so that its own homeostatic mechanisms can more easily return things to normal. One potentially tweakable process is the Wnt signaling pathway, a soluble ligand-receptor system that controls transcription of β-catenin and other genes. This pathway is used over and over again for specification of the body axis and morphogenesis during development and goes awry in cancer. Minear and colleagues noted that Wnt signaling participates in regrowth and healing of broken bones and found a way to augment its action. Their treatment accelerates natural recovery from bone injury.

The authors used genetically altered mice to show that Wnt signaling is increased in regions in which bone is healing, which suggests that it participates in the bone regeneration process. By interfering with the action of a Wnt signaling inhibitor, they potentiated this pathway even more, which resulted in more rapid healing of small holes that they made in the tibial bone of the mice.

To begin to translate these results to patients, the authors then increased Wnt signaling in these mice with an approach that, unlike genetic manipulation, could be replicated in the clinic. Getting around the fact that Wnt ligands are insoluble in aqueous solution by using a liposome package, the authors applied Wnt-filled liposomes to healing bone and again showed faster healing. The basis of this effect was both the simulation of skeletal progenitor cell proliferation and the promotion of differentiation of these progenitors into osteoblasts, the cellular builder of bone.

Wnt packaged in lipid membrane vesicles could have advantages over other treatments that can facilitate bone healing, specifically bone morphogenetic protein, because of the advantageous type of bone that is created. And the fact that the Wnt pathway controls numerous fundamental processes may mean that Wnt-containing vesicles could prove useful in tweaking other systems to help the body more rapidly achieve healing and homeostasis.

Footnotes

  • * These authors contributed equally to this work.

  • Received June 26, 2009.
  • Accepted April 9, 2010.