BMP‐2 modulates β‐catenin signaling through stimulation of <i>Lrp5</i> expression and inhibition of β‐TrCP expression in osteoblasts

Abstract

Canonical BMP and Wnt signaling pathways play critical roles in regulation of osteoblast function and bone formation. Recent studies demonstrate that BMP-2 acts synergistically with beta-catenin to promote osteoblast differentiation. To determine the molecular mechanisms of the signaling cross-talk between canonical BMP and Wnt signaling pathways, we have used primary osteoblasts and osteoblast precursor cell lines 2T3 and MC3T3-E1 cells to investigate the effect of BMP-2 on beta-catenin signaling. We found that BMP-2 stimulates Lrp5 expression and inhibits the expression of beta-TrCP, the F-box E3 ligase responsible for beta-catenin degradation and subsequently increases beta-catenin protein levels in osteoblasts. In vitro deletion of the beta-catenin gene inhibits osteoblast proliferation and alters osteoblast differentiation and reduces the responsiveness of osteoblasts to the BMP-2 treatment. These findings suggest that BMP-2 may regulate osteoblast function in part through modulation of the beta-catenin signaling.