Wnt Proteins Promote Bone Regeneration
- Steven Minear1,*,
- Philipp Leucht1,2,*,
- Jie Jiang1,*,
- Bo Liu1,
- Arial Zeng3,
- Christophe Fuerer3,
- Roel Nusse3,† and
- Jill A. Helms1,†
- 1Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford School of Medicine, Stanford, CA 94305, USA.
- 2Department of Orthopaedic Surgery, Stanford School of Medicine, Stanford, CA 94305, USA.
- 3Howard Hughes Medical Institute, Department of Developmental Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
- †To whom correspondence should be addressed. E-mail: rnusse{at}stanford.edu (R.N.); jhelms{at}stanford.edu (J.A.H.)
Abstract
The Wnt signaling pathway plays a central role in bone development and homeostasis. In most cases, Wnt ligands promote bone growth, which has led to speculation that Wnt factors could be used to stimulate bone healing. We gained insights into the mechanism by which Wnt signaling regulates adult bone repair through the use of the mouse strain Axin2LacZ/LacZ in which the cellular response to Wnt is increased. We found that bone healing after injury is accelerated in Axin2LacZ/LacZ mice, a consequence of more robust proliferation and earlier differentiation of skeletal stem and progenitor cells. In parallel, we devised a biochemical strategy to increase the duration and strength of Wnt signaling at the sites of skeletal injury. Purified Wnt3a was packaged in liposomal vesicles and delivered to skeletal defects, where it stimulated the proliferation of skeletal progenitor cells and accelerated their differentiation into osteoblasts, cells responsible for bone growth. The end result was faster bone regeneration. Because Wnt signaling is conserved in mammalian tissue repair, this protein-based approach may have widespread applications in regenerative medicine.
Footnotes
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↵* These authors contributed equally to this work.
- Received June 26, 2009.
- Accepted April 9, 2010.
- Copyright © 2010, American Association for the Advancement of Science
