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β-Catenin—A supporting role in the skeleton

Authors

  • Natasha Case,

    1. Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599
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  • Janet Rubin

    Corresponding author
    1. Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599
    2. Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599
    • Department of Medicine, University of North Carolina, 5032 Burnett-Womack, CB #7170, Chapel Hill, NC 27599.
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Abstract

In the last 5 years a role for β-catenin in the skeleton has been cemented. Beginning with mutations in the Lrp5 receptor that control β-catenin canonical downstream signals, and progressing to transgenic models with bone-specific alteration of β-catenin, research has shown that β-catenin is required for normal bone development. A cell critical to bone in which β-catenin activity determines function is the marrow-derived mesenchymal stem cell (MSC), where sustained β-catenin prevents its distribution into adipogenic lineage. β-Catenin actions are less well understood in mature osteoblasts: while β-catenin contributes to control of osteoclastic bone resorption via alteration of the osteoprotegerin/RANKL ratio, a specific regulatory role during osteoblast bone synthesis has not yet been determined. The proven ability of mechanical factors to prevent β-catenin degradation and induce nuclear translocation through Lrp-independent mechanisms suggests processes by which exercise might modulate bone mass via control of lineage allocation, in particular, by preventing precursor distribution into the adipocyte pool. Effects resulting from mechanical activation of β-catenin in mature osteoblasts and osteocytes likely modulate bone resorption, but whether β-catenin is involved in osteoblast synthetic function remains to be proven for both mechanical and soluble mediators. As β-catenin appears to support the downstream effects of multiple osteogenic factors, studies clarifying when and where β-catenin effects occur will be relevant for translational approaches aimed at preventing bone loss and terminal adipogenic conversion. J. Cell. Biochem. 110: 545–553, 2010. © 2010 Wiley-Liss, Inc.

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