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J Cell Biochem. 2005 Feb 1;94(2):403-18.

Beta-catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation.

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Division of Bone and Mineral Diseases, Department of Internal Medicine, St. Louis, Missouri 63110, USA.


Mutations of critical components of the Wnt pathway profoundly affect skeletal development and maintenance, probably via modulation of beta-catenin signaling. We tested the hypothesis that beta-catenin is involved in mesenchymal lineage allocation to osteogenic cells using a beta-catenin mutant with constitutive transcriptional activity (DeltaN151). Although this stable beta-catenin had no effects by itself on osteogenic differentiation of multipotent embryonic cell lines, it synergized with bone morphogenetic protein-2 (BMP-2) resulting in dramatic stimulation of alkaline phosphatase activity, osteocalcin gene expression, and matrix mineralization. Likewise, DeltaN151 and BMP-2 synergistically stimulated new bone formation after subperiosteal injection in mouse calvaria in vivo. Conversely, DeltaN151 prevented adipogenic differentiation from pre-adipocytic or uncommitted mesenchymal cells in vitro. Intriguingly, the synergism with BMP-2 on gene transcription occurred without altering expression of Cbfa1/Runx2, suggesting actions independent or downstream of this osteoblast-specific transcription factor. Thus, beta-catenin directs osteogenic lineage allocation by enhancing mesenchymal cell responsiveness to osteogenic factors, such as BMP-2, in part via Tcf/Lef dependent mechanisms. In vivo, this synergism leads to increased new bone formation.

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