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β-Catenin in the race to fracture repair: in it to Wnt

Nature Clinical Practice Rheumatology volume 4, pages 413–419 (2008)Cite this article

Abstract

The Wnt/β-catenin pathway regulates multiple biological events during embryonic development, including bone formation. Fracture repair recapitulates some of the processes of normal bone development, such as the formation of bone from a cartilaginous template, and many cell-signaling pathways that underlie bone development are activated during the repair process. The Wnt/β-catenin signaling pathway is activated during fracture repair, and dysregulation of this pathway alters the normal bone-healing response. In early pluripotent mesenchymal stem cells, Wnt/β-catenin signaling needs to be precisely regulated to facilitate the differentiation of osteoblasts; by contrast, β-catenin is not needed for chondrocyte differentiation. Once mesenchymal stem cells are committed to the osteoblast lineage, activation of Wnt/β-catenin signaling enhances bone formation. This activity suggests that the Wnt/β-catenin pathway is a therapeutic target during bone repair. Indeed, treatments that activate Wnt/β-catenin signaling, such as lithium, increase bone density and also enhance healing.

Key Points

  • Wnt/β-catenin signaling has a major role in embryonic bone development by controlling the differentiation of pluripotent mesenchymal stem cells into osteoblasts

  • Activation of the Wnt/β-catenin pathway during embryonic bone development increases bone formation

  • Wnt/β-catenin signaling is activated during fracture repair

  • Removal of β-catenin prevents osteochondral progenitor cells from differentiating into osteoblasts

  • Activation of β-catenin by pharmacologic agents such as lithium can enhance fracture repair and improve patient outcome

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Figure 1: The Wnt/β-catenin signaling pathway.
Figure 2: The role of β-catenin in different cell types during fracture repair.

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Authors and Affiliations

  1. D Silkstone and H Hong are graduate students and BA Alman is the AJ Latner Chair of Orthopaedic Surgery at the University of Toronto, Toronto, ON, Canada.,

    David Silkstone, Helen Hong & Benjamin A Alman

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  1. David Silkstone
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  2. Helen Hong
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  3. Benjamin A Alman
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Correspondence to Benjamin A Alman.

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Silkstone, D., Hong, H. & Alman, B. β-Catenin in the race to fracture repair: in it to Wnt. Nat Rev Rheumatol 4, 413–419 (2008). https://doi.org/10.1038/ncprheum0838

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  • DOI: https://doi.org/10.1038/ncprheum0838

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