Profilin Expression Is Regulated by Bone Morphogenetic Protein (BMP) in Osteoblastic Cells
Profilin Expression Is Regulated by Bone Morphogenetic Protein (BMP) in Osteoblastic Cells
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DOI：
10.1002/jcb.25310
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发表时间：
2016-03
影响因子：
4
通讯作者：
Wanting Lin;Y. Ezura;Y. Izu;Smriti Aryal A.C;Makiri Kawasaki;Pawaputanon Na Mahasarakham Chantida;K. Moriyama;M. Noda
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作者：
Wanting Lin;Y. Ezura;Y. Izu;Smriti Aryal A.C;Makiri Kawasaki;Pawaputanon Na Mahasarakham Chantida;K. Moriyama;M. Noda
Profilin 1（Pfn1）调节细胞骨架重组和迁移，但其在成骨细胞中的作用尚不清楚。骨形态发生蛋白（BMP）是一种多功能的细胞因子，参与成骨细胞分化，促进骨再生和修复。虽然已知有几种分子可以调节BMP信号，但决定BMP在成骨细胞功能中作用水平的机制仍不完全清楚。因此，我们研究了Pfn1在成骨细胞中的表达及其在BMP诱导的成骨细胞分化中的作用。在成骨细胞MC3T3-E1（MC）中，Pfn 1 mRNA组成性表达，其表达水平在培养过程中以时间依赖性方式下降，与碱性磷酸酶活性的增加相反，表明Pfn 1表达沿着分化而下调。为了进一步测试成骨细胞分化对Pfn1表达的影响，用BMP处理MC细胞。BMP处理抑制Pfn1 mRNA的水平。BMP的这种抑制作用是时间依赖性的，并且当BMP处理持续较长时间时，观察到Pfn1 mRNA水平的进一步下调。siRNA敲低Pfn1 mRNA（KD）可增强MC细胞中BMP诱导的碱性磷酸酶（Alp）活性增加。为了分析调节机制，检查Alp mRNA水平，Pfn1 KD增强BMP诱导的Alp mRNA表达水平的增加。此外，Pfn1 KD通过成骨细胞中的BMP反应元件增强BMP诱导的荧光素酶报告基因活性的转录表达。这些数据表明Pfn1是BMP的新靶点，并且至少部分地通过转录事件抑制BMP诱导的成骨细胞分化。J.细胞。117：621 - 628，2016.© 2015威利期刊公司.
Profilin 1 (Pfn1) regulates cytoskeletal reorganization and migration, but its role in osteoblasts is not known. BMP (bone morphogenetic protein) is a multifunctional cytokine involved in osteoblastic differentiation and promotes bone regeneration and repair. Although several molecules are known to modulate BMP signaling, mechanisms that determine the levels of BMP action in osteoblastic function are still incompletely understood. We therefore examine the expression of Pfn1 in osteoblasts and its role in BMP‐induced differentiation in osteoblasts. In osteoblastic MC3T3‐E1(MC) cells, Pfn1 mRNA is expressed constitutively and its expression levels are declined during the culture in a time dependent manner in contrast to the increase in alkaline phosphatase activity revealing that Pfn1 expression is down regulated along with differentiation. To test the effects of osteoblastic differentiation on Pfn1expression further, MC cells are treated with BMP. BMP treatment suppresses the levels of Pfn1 mRNA. This suppressive effect of BMP is time dependent and further down regulation of Pfn1 mRNA levels is observed when the BMP treatment is continued for a longer period of time. Pfn1mRNA knock down (KD) by siRNAs enhances BMP‐induced increase in alkaline phosphatase (Alp) activity in MC cells. To analyze the regulatory mechanism, Alp mRNA levels are examined and Pfn1 KD enhances the BMP‐induced increase in the levels of Alp mRNA expression. Furthermore, Pfn1 KD enhances BMP‐induced transcriptional expression of luciferase reporter activity via BMP response element in osteoblasts. These data indicate that Pfn1 is a novel target of BMP and suppresses BMP‐induced differentiation of osteoblasts at least in part via transcriptional event. J. Cell. Biochem. 117: 621–628, 2016. © 2015 Wiley Periodicals, Inc.