BMP-2 modulates β-catenin signaling through stimulation of Lrp5 expression and inhibition of β-TrCP expression in osteoblasts

Ming Zhang, Ying Yan, Yong Bin Lim, Dezhi Tang, Rong Xie, Ann Chen, Peter Tai, Stephen E. Harris, Lianping Xing, Yi Xian Qin, Di Chen

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)896-905
Number of pages10
JournalJournal of Cellular Biochemistry
Volume108
Issue number4
DOIs
StatePublished - Nov 1 2009

Keywords

  • BMP-2
  • LRP5
  • Osteoblast differentiation
  • β-TrCP
  • β-catenin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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