Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis.
Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis.
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DOI：
10.1038/srep04493
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发表时间：
2014-03-27
影响因子：
4.6
通讯作者：
Kobayashi Y
中科院分区：
文献类型：
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作者：
Okamoto M;Udagawa N;Uehara S;Maeda K;Yamashita T;Nakamichi Y;Kato H;Saito N;Minami Y;Takahashi N;Kobayashi Y
Wnt通过β-catenin依赖的经典和β-catenin非依赖的非经典信号通路调节骨形成。然而，成骨细胞发生过程中两种信号通路之间的合作仍有待阐明。在这里，我们发现成骨细胞系中Wnt 5a的缺乏损害了Wnt/β-catenin信号传导，这是由于Lrp 5和Lrp 6的表达减少。ST 2细胞，一种基质细胞系，用Wnt 5a预处理增强经典Wnt配体诱导的Tcf/Lef转录活性。短发夹RNA介导的Wnt 5a敲低，而不是用Wnt/β-catenin信号传导的拮抗剂Dkk 1处理，降低了成骨细胞系细胞在成骨培养条件下Lrp 5和Lrp 6的表达。来自Wnt 5a缺陷小鼠的成骨细胞系细胞表现出减少的Wnt/β-连环蛋白信号传导，其损害成骨细胞分化并增强脂肪细胞分化。腺病毒介导的Lrp 5基因转移到Wnt 5a缺陷的成骨细胞系细胞中拯救了它们的表型特征。因此，Wnt 5a诱导的非经典信号传导与Wnt/β-连环蛋白信号传导合作以实现适当的骨形成。
Wnt regulates bone formation through β-catenin-dependent canonical and -independent noncanonical signaling pathways. However, the cooperation that exists between the two signaling pathways during osteoblastogenesis remains to be elucidated. Here, we showed that the lack of Wnt5a in osteoblast-lineage cells impaired Wnt/β-catenin signaling due to the reduced expression of Lrp5 and Lrp6. Pretreatment of ST2 cells, a stromal cell line, with Wnt5a enhanced canonical Wnt ligand-induced Tcf/Lef transcription activity. Short hairpin RNA-mediated knockdown of Wnt5a, but not treatment with Dkk1, an antagonist of Wnt/β-catenin signaling, reduced the expression of Lrp5 and Lrp6 in osteoblast-lineage cells under osteogenic culture conditions. Osteoblast-lineage cells from Wnt5a-deficient mice exhibited reduced Wnt/β-catenin signaling, which impaired osteoblast differentiation and enhanced adipocyte differentiation. Adenovirus-mediated gene transfer of Lrp5 into Wnt5a-deficient osteoblast-lineage cells rescued their phenotypic features. Therefore, Wnt5a-induced noncanonical signaling cooperates with Wnt/β-catenin signaling to achieve proper bone formation.
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影响因子：
4.8
作者：
Nakashima, A;Katagiri, T;Tamura, M
通讯作者：
Tamura, M
影响因子：
2.1
作者：
Oishi, I;Suzuki, H;Minami, Y
通讯作者：
Minami, Y
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
影响因子：
82.9
作者：
通讯作者：
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