FGF Suppresses Poldip2 Expression in Osteoblasts
FGF Suppresses Poldip2 Expression in Osteoblasts
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DOI：
10.1002/jcb.25813
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发表时间：
2017-07-01
影响因子：
4
通讯作者：
Ezura, Yoichi
中科院分区：
文献类型：
--
作者：
Katsumura, Sakie;Izu, Yayoi;Ezura, Yoichi
骨质疏松症是现代世界中最常见的与衰老相关的疾病之一。尽管人们对骨质疏松症的发病机制进行了多方面的研究，但骨量丢失的病理生理机制仍不完全清楚。Poldip2是一种已被证明参与血管细胞迁移和血管生成的分子。然而，Poldip2在骨细胞中的表达及其调控尚不清楚。因此，我们研究了成骨细胞中Poldip2mRNA的表达以及骨调节剂对Poldip2表达的影响。我们发现Poldip2基因在成骨细胞MC3T3-E1中有表达。作为成骨细胞和血管生成的调控因子，研究了成骨细胞中成纤维细胞生长因子的调控作用。成纤维细胞生长因子抑制MC3T3-E1细胞Poldip2的表达，呈时间依赖性。蛋白质合成抑制剂而不是转录抑制剂降低了成纤维细胞生长因子对MC3T3-E1细胞Poldip2基因表达的影响。在骨相关激素方面，地塞米松可促进成骨细胞MC3T3-E1中Poldip2的表达，而成纤维细胞生长因子仍可抑制这种作用。在功能方面，siRNA敲除Poldip2抑制了MC3T3-E1细胞的迁移。Poldip2在原代培养的成骨细胞中也有表达，成纤维细胞生长因子也抑制了Poldip2的表达。最后，Poldip2在体内的股骨中表达，与年轻成年小鼠相比，老年小鼠的Poldip2水平升高。这些数据表明，Poldip2在成骨细胞中表达，是成纤维细胞生长因子的靶点之一。(C)2016威利期刊公司。
Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modernworld. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cellmigration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cellswere not known. Therefore, we examined the Poldip2mRNAexpression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulationwas investigated in these cells. FGF suppressed the expression of Poldip2 inMC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed themigration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. (C) 2016 Wiley Periodicals, Inc.