Beta-catenin--a supporting role in the skeleton.
In the last 5 years a role for beta-catenin in the skeleton has been cemented. Beginning with mutations in the Lrp5 receptor that control beta-catenin canonical downstream signals, and progressing to transgenic models with bone-specific alteration of beta-catenin, research has shown that beta-catenin is required for normal bone development. A cell critical to bone in which beta-catenin activity determines function is the marrow-derived mesenchymal stem cell (MSC), where sustained beta-catenin prevents its distribution into adipogenic lineage. beta-Catenin actions are less well understood in mature osteoblasts: while beta-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 beta-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 beta-catenin in mature osteoblasts and osteocytes likely modulate bone resorption, but whether beta-catenin is involved in osteoblast synthetic function remains to be proven for both mechanical and soluble mediators. As beta-catenin appears to support the downstream effects of multiple osteogenic factors, studies clarifying when and where beta-catenin effects occur will be relevant for translational approaches aimed at preventing bone loss and terminal adipogenic conversion.
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Natasha
N
Case
Janet
J
Rubin
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D012863:Skeleton; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin