Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis.
Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis.
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DOI：
10.1016/j.bbrc.2012.05.039
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发表时间：
2012-06
影响因子：
3.1
通讯作者：
E. Nemoto;Yukari Ebe;S. Kanaya;M. Tsuchiya;Takashi Nakamura;M. Tamura;H. Shimauchi
中科院分区：
文献类型：
--
作者：
E. Nemoto;Yukari Ebe;S. Kanaya;M. Tsuchiya;Takashi Nakamura;M. Tamura;H. Shimauchi
Wnt 是分泌性糖蛋白，通过依赖 β-连环蛋白的经典途径和不依赖 β-连环蛋白的非经典途径调节细胞过程（包括增殖、分化和凋亡），从而介导发育和发育后生理学。据报道，Wnt5a 通过受体酪氨酸激酶样孤儿受体 2 (Ror2) 激活非经典 Wnt 信号传导。尽管 Wnt5a/Ror2 信号传导似乎支持正常的骨生理学，但非经典 Wnt 在成骨中的生物学意义本质上是未知的。在这项研究中，我们通过免疫组织化学方法鉴定了胫骨生长板骨化区以及大鼠胫骨骨髓中成骨细胞中 Wnt5a 的表达。此外，我们使用培养的前成骨细胞 MC3T3-E1 细胞表明，BMP-2 介导的成骨细胞分化与 Wnt5a 和 Ror2 表达增加相关。沉默 MC3T3-E1 细胞中 Wnt5a 和 Ror2 的基因表达会导致 BMP-2 介导的成骨细胞分化受到抑制，表明 Wnt5a 和 Ror2 信号传导对于 BMP-2 介导的成骨细胞分化至关重要。在siWnt5a处理的细胞和对照细胞中，BMP-2刺激以相似的方式诱导Smad1/5/8的磷酸化，这表明Wnt5a对于BMP-2对Smads的磷酸化来说是可有可无的。综上所述，我们的结果表明 Wnt5a/Ror2 信号传导似乎以 Smad 独立途径参与 BMP-2 介导的成骨细胞分化。
Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology by regulating cellular processes including proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathway. It has been reported that Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal bone physiology, the biological significance of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified expression of Wnt5a in osteoblasts in the ossification zone of the tibial growth plate as well as bone marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show that osteoblastic differentiation mediated by BMP-2 is associated with increased expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells. Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a similar fashion in both siWnt5a-treated cells and control cells, suggesting that Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together, our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2-mediated osteoblast differentiation in a Smad independent pathway.