Department of Orthopaedics, Center for Musculoskeletal Research, Rochester, New York 14642, USA.
J Cell Biochem. 2009 Nov 1;108(4):896-905. doi: 10.1002/jcb.22319.
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.
经典 BMP 和 Wnt 信号通路在调节成骨细胞功能和骨形成中发挥着关键作用。最近的研究表明，BMP-2 与β-catenin 协同作用促进成骨细胞分化。为了确定经典 BMP 和 Wnt 信号通路之间信号转导的分子机制，我们使用原代成骨细胞和成骨细胞前体细胞系 2T3 和 MC3T3-E1 细胞来研究 BMP-2 对β-catenin 信号的影响。我们发现 BMP-2 刺激 Lrp5 的表达并抑制β-TrCP 的表达，β-TrCP 是负责β-catenin 降解的 F -box E3 连接酶，从而增加成骨细胞中的β-catenin 蛋白水平。体外敲除β-catenin 基因抑制成骨细胞增殖并改变成骨细胞分化，降低成骨细胞对 BMP-2 处理的反应性。这些发现表明，BMP-2 可能通过调节β-catenin 信号来调节成骨细胞功能。
