Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt
Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt
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DOI：
10.1159/000430319
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Wang, Bomin
中科院分区：
文献类型：
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作者：
Wang, Dawei;Ma, Wenpu;Wang, Bomin
背景/目的：柚皮苷是柑橘类水果中天然存在的一种化合物，已被阐明具有促进骨骼发育和维持的作用。方法：采用体外成骨样UMR-106细胞模型和体内摘除卵巢模拟骨质疏松模型，研究柚皮苷的生物学作用。由于Wnt/β-catenin信号转导参与成骨细胞的形成，因此研究了柚皮苷对Wnt/β-catenin信号转导的影响。结果：柚皮苷可促进UMR-106细胞β-连环素的表达，促进Ser552对β-连环素的磷酸化，从而激活淋巴增强因子(Lef)/T细胞因子(Tcf)转录因子。蛋白激酶B(Akt)抑制剂(Akti-1/2)和AMP激活的蛋白激酶(AMPK)抑制剂(多索吗啡)可减弱柚皮苷对β-连环素磷酸化的影响，提示柚皮苷通过调节Akt和AMPK而激活β-连环素。在去卵巢(OVX)小鼠中，柚皮苷治疗可提高骨强度，而AMPK和Akt抑制剂部分逆转了这一作用，进一步证实了Akt和AMPK参与了柚皮苷的体内作用。结论：我们的研究指出了关于柚皮苷通过Akt和AMPK信号通路促进骨形成机制的新发现。版权所有(C)2015年S.Karger AG，巴塞尔
Background/Aims: Naringin is a naturally existing compound in citrus fruits and has been elucidated to promote bone development and maintenance. Methods: The biological roles of naringin were investigated in vitro using osteoblast-like UMR-106 cells, and in vivo through performing ovariectomy to mimic osteoporosis in female mice. Since Wnt/beta-catenin signaling is involved in osteoblastogenesis, the effect of naringin on Wnt/beta-catenin signaling was studied. Results: Naringin promoted the mRNA and protein expressions of beta-catenin, and improved Ser552 phosphorylation on beta-catenin in UMR-106 cells, which leads to the activation of lymphoid enhancer factor (LEF)/T-cell factor (TCF) transcription factors. The recruitments of protein kinase B (Akt) inhibitor (Akti-1/2) and AMP-activated protein kinase (AMPK) inhibitor (Dorsomorphin) reduced the influence of naringin on beta-catenin phosphorylation, suggesting naringin activates beta-catenin via regulating Akt and AMPK. In ovariectomized (OVX) mice naringin treatment improved the bone strength while AMPK and Akt inhibitors partly reversed the effect, which further proved the involvements of Akt and AMPK in the action of naringin in vivo. Conclusion: Our study points to a novel finding on the mechanism of naringin in facilitating bone formation via Akt and AMPK signaling. Copyright (C) 2015 S. Karger AG, Basel