BMP-2 modulates beta-catenin signaling through stimulation of Lrp5 expression and inhibition of beta-TrCP expression in osteoblasts.
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.
Zhang
Ming
M
Department of Orthopaedics, Center for Musculoskeletal Research, Rochester, New York 14642, USA.
Yan
Ying
Y
Lim
Yong-Bin
YB
Tang
Dezhi
D
Xie
Rong
R
Chen
Ann
A
Tai
Peter
P
Harris
Stephen E
SE
Xing
Lianping
L
Qin
Yi-Xian
YX
Chen
Di
D
D016475:3T3 Cells; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D026502:LDL-Receptor Related Proteins / Q000378:metabolism*; D008024:Ligands; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D055396:Bone Morphogenetic Protein 2; D026502:LDL-Receptor Related Proteins; D008024:Ligands; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins