FGF2 crosstalk with Wnt signaling in mediating the anabolic action of PTH on bone formation.
FGF2 crosstalk with Wnt signaling in mediating the anabolic action of PTH on bone formation.
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FGF2 与 Wnt 信号传导串扰介导 PTH 对骨形成的合成代谢作用。
DOI：
10.1016/j.bonr.2018.09.003
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发表时间：
2018
期刊：
影响因子：
2.5
通讯作者：
Hurley,MarjaM
中科院分区：
文献类型：
--
作者：
Xiao,Liping;Fei,Yurong;Hurley,MarjaM
甲状旁腺激素（PTH）在骨中的合成代谢作用的机制尚未完全确定。PTH的骨合成代谢作用需要成纤维细胞生长因子2（FGF 2）以及Wnt信号传导，并且FGF 2调节成骨细胞中的Wnt信号传导。在野生型（WT）和Fgf 2敲除的小鼠（Fgf 2KO）的骨中，体内PTH施用差异性地调节Wnt信号传导。PTH增加WT小鼠Wnt 10 b mRNA和蛋白，但在KO小鼠中不增加。KO组Wnt拮抗剂SOST mRNA和蛋白表达明显高于对照组。然而，PTH在WT和Fgf 2KO小鼠中显著降低Sost mRNA，但在Fgf 2KO小鼠中降低程度较小。Dickhopf 2（DKK 2）是成骨细胞矿化的关键。PTH使WT小鼠Dkk 2 mRNA表达增加，但Fgf 2KO小鼠Dkk 2 mRNA表达减少。PTH显著增加WT小鼠Lrp 5 mRNA表达和Lrp 6磷酸化水平，但Fgf 2KO小鼠Lrp 5 mRNA表达和Lrp 6磷酸化水平显著降低。PTH显著增加WT小鼠β-catenin表达和Wnt/β-catenin转录活性，但在Fgf 2KO小鼠中无此作用。这些数据表明，受损的骨合成代谢反应PTH在Fgf 2KO小鼠是部分介导的减弱Wnt信号。
The mechanisms of the anabolic effect of parathyroid hormone (PTH) in bone are not fully defined. The bone anabolic effects of PTH require fibroblast growth factor 2 (FGF2) as well as Wnt signaling and FGF2 modulates Wnt signaling in osteoblasts. In vivo PTH administration differentially modulated Wnt signaling in bones of wild type (WT) and in mice that Fgf2 was knocked out (Fgf2KO). PTH increased Wnt10b mRNA and protein in WT but not in KO mice. Wnt antagonist SOST mRNA and protein was significantly higher in KO group. However, PTH decreased Sost mRNA significantly in WT as well as inFgf2KOmice, but to a lesser extent inFgf2KO. Dickhopf 2 (DKK2) is critical for osteoblast mineralization. PTH increasedDkk2mRNA in WT mice but the response was impaired inFgf2KOmice. PTH significantly increased Lrp5 mRNA and phosphorylation of Lrp6 in WT but the increase was markedly attenuated inFgf2KOmice. PTH increased β-catenin expression and Wnt/β-catenin transcriptional activity significantly in WT but not inFgf2KOmice. These data suggest that the impaired bone anabolic response to PTH inFgf2KOmice is partially mediated by attenuated Wnt signaling.