BMP‐2 modulates β‐catenin signaling through stimulation of Lrp5 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 β-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 β-catenin signaling. We found that BMP-2 stimulates Lrp5 expression and inhibits the expression of β-TrCP, the F-box E3 ligase responsible for β-catenin degradation and subsequently increases β-catenin protein levels in osteoblasts. In vitro deletion of the β-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 β-catenin signaling.

Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

“…The absence of Lrp5 specifically depletes adult regenerative stem cell activity to less than 1% [48]. It has been shown that an increased expression of Lrp5 is sufficient for activation of the canonical Wnt signaling pathway [49]. In light of our data showing that low oxygen increased Lrp5 mRNA transcript levels (Fig.…”

β-Catenin is essential for Müllerian duct regression during male sexual differentiation

“…Bmp2 also regulates -catenin signaling pathway during bone formation (Chen et al, 2007;Zhang et al, 2009). Regulation of the canonical WNT/-catenin pathway by TGF-/BMP signaling is an important regulatory mechanism for a number of biological processes.…”

Effects of Exercise on Low Density Lipoprotein Receptor Related Protein 5 Gene Expression in Patients With Postmenopausal Osteoporosis

“…They also suggested that the contributory effect of this up-regulation of LRP5 by 1,25(OH) 2 D 3 to the overall actions of 1,25(OH) 2 D 3 on bone remained to be determined. 35 Actually, if there is such an interaction between vitamin D and LRP5 gene expression, this might have at least partially played some part in the variation of our patients' LRP5 expression patterns.…”

“…It has been demonstrated that the expression of LRP5 in osteoblast was increased by bone morphogenetic protein 2. 35 Fretz et al 36 discovered that 1,25(OH) 2 D 3 may induce binding of the vitamin D receptor to sites within the LRP5 gene locus. This interaction is thought to cause a modification in chromatin structure within the LRP5 locus and induce LRP5 messenger ribonucleic acid transcription in osteoblasts.…”