BMP‐2 modulates β‐catenin signaling through stimulation of Lrp5 expression and inhibition of β‐TrCP expression in osteoblasts |
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| Authors: | 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 |
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| Affiliation: | 1. Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, Rochester, New York 14642;2. Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China;3. Department of Pathology, University of Rochester School of Medicine, Rochester, New York 14642;4. Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229;5. Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York 11794 |
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| 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. J. Cell. Biochem. 108: 896–905, 2009. © 2009 Wiley‐Liss, Inc. |
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| Keywords: | BMP‐2 β ‐catenin LRP5 β ‐TrCP osteoblast differentiation |
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