Angiopoietin-like protein 2 is a positive regulator of osteoblast differentiation.
Angiopoietin-like protein 2 is a positive regulator of osteoblast differentiation.
复制标题
DOI：
10.1016/j.metabol.2017.01.006
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Aiko Takano;T. Fukuda;T. Shinjo;M. Iwashita;E. Matsuzaki;Ken Yamamichi;Masaaki Takeshita;T. Sanui;F. Nishimura
中科院分区：
文献类型：
--
作者：
Aiko Takano;T. Fukuda;T. Shinjo;M. Iwashita;E. Matsuzaki;Ken Yamamichi;Masaaki Takeshita;T. Sanui;F. Nishimura
简介和目的多项研究报道，血管生成素样蛋白 2 (Angptl2) 在脂肪细胞中大量表达，并且与脂肪组织炎症相关。在本研究中，我们发现成骨细胞和间充质干细胞也高水平表达Angptl2。本研究的目的是了解Angptl2在成骨细胞分化中的作用。方法检测Angptl2在成骨细胞和脂肪细胞分化过程中的表达。使用Angptl2小干扰核糖核酸(siRNA)通过基因敲除分析Angptl2对细胞分化和相关信号传导的作用。结果Angptl2在MC3T3-E1细胞、ST2细胞和原代成骨细胞中高表达，但在RAW264细胞中不高表达。使用siRNA抑制Angptl2表达可显着抑制MC3T3-E1、ST2细胞和原代成骨细胞中的碱性磷酸酶(ALP)表达和成骨细胞分化。 Angptl2 siRNA 还抑制 ST2 细胞中的脂肪细胞分化。用 Angptl2 siRNA 处理 MC3T3-E1 细胞，导致多种细胞信号通路活性下调，包括细胞外信号调节激酶 (ERK)、Jun 氨基末端激酶 (JNK)、Akt 和核因子 kappa B (NF-κB) 信号。它还下调了 Osterix 的表达，但不下调 runt 相关转录因子 2 (Runx2) 的表达，表明 Angptl2 是 Osterix 及其下游信号的正激活剂。用抗 Angptl2 抗体处理 MC3T3-E1 细胞可抑制 ALP 基因表达。此外，用正常MC3T3-E1细胞的培养上清液处理Angptl2 siRNA处理的细胞可以恢复ALP基因表达，表明Angptl2以自分泌方式发挥作用。结论结果表明Angptl2是细胞分化的自分泌正调节因子。因此，表明Angptl2不仅调节脂肪组织代谢，还调节骨代谢。
Introduction and AimsSeveral studies have reported that angiopoietin-like protein 2 (Angptl2) is expressed abundantly in adipocytes and is associated with adipose tissue inflammation. In the present study, we found that osteoblasts and mesenchymal stem cells also expressed Angptl2 at high levels. The aim of this study was to understand the role of Angptl2 in osteoblastic cell differentiation.MethodsAngptl2 expression was examined during osteoblast and adipocyte differentiation. The role of Angptl2 on cell differentiation and associated signaling was analyzed by gene knockdown using Angptl2 small interfering ribonucleic acid (siRNA).ResultsAngptl2 was highly expressed in MC3T3-E1 cells, ST2 cells and primary osteoblasts, but not in RAW264 cells. Inhibition of Angptl2 expression using siRNA markedly inhibited alkaline phosphatase (ALP) expression and osteoblastic differentiation in MC3T3-E1, ST2 cells and primary osteoblasts. Angptl2 siRNA also inhibited adipocyte differentiation in ST2 cells. Treatment of MC3T3-E1 cells with Angptl2 siRNA led to the down-regulation of the activities of several cell signaling pathways, including extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK), Akt, and nuclear factor kappa B (NF-κB) signals. It also down-regulated the expression of Osterix, but not that of runt-related transcription factor 2 (Runx2), suggesting that Angptl2 is a positive activator of Osterix and its down-stream signals. Treatment of MC3T3-E1 cells with anti-Angptl2 antibodies suppressed ALP gene expression. In addition, treatment of Angptl2 siRNA-treated cells with culture supernatants of normal MC3T3-E1 cells restored ALP gene expression, indicating that Angptl2 acts in an autocrine manner.ConclusionsThe results suggest that Angptl2 is an autocrine positive regulator of cell differentiation. Thus, it is suggested that Angptl2 regulates not only adipose tissue metabolism but also bone metabolism.