Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: Implications for the study of mechanosensation in bone.
Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: Implications for the study of mechanosensation in bone.
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DOI：
10.1016/j.bone.2010.08.007
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发表时间：
2010-11
期刊：
影响因子：
4.1
通讯作者：
Johnson, Mark L.
中科院分区：
文献类型：
--
作者：
Kamel, Mohamed A.;Picconi, Jason L.;Lara-Castillo, Nuria;Johnson, Mark L.
骨细胞被假设为骨中的机械感觉细胞。然而，成骨细胞模型已最常用于研究骨中的机械感觉机制。因此，我们试图确定骨细胞和成骨细胞模型之间是否存在差异，相对于MLO-Y 4骨细胞、2 T3成骨细胞和原代新生儿颅骨细胞（NCC）中响应脉动流体流动剪切应力（PFVSS）的β-连环蛋白信号传导的活化。在MLO-Y 4细胞中，在2和16 dynes/cm 2 PFFS下观察到β-连环蛋白核转位，但在2 T3或NCC培养物中仅在16 dynes/cm 2下观察到β-连环蛋白核转位。MLO-Y 4细胞在所有水平的PFFSS（2-24达因/cm 2）下向培养基中释放大量的PGE 2，并且我们观察到相对于PFFSS水平的双相模式。相反，2 T3细胞的PGE 2释放仅在>1小时开始的16和24达因/cm 2 PFFS期间检测到，并且从未达到MLO-Y 4细胞产生的水平。外源性添加的PGE 2能够在所有细胞中诱导β-连环蛋白核转位，表明观察到的细胞系之间的β-连环蛋白核转位差异与PGE 2产生的差异相关。为了研究MLO-Y 4和2 T3细胞PGE 2释放差异的可能机制，我们检测了PFFSS对Ptgs 2（考克斯-2）基因表达的调节。2 T3细胞Ptgs 2 mRNA水平在PFFS 2小时后0和24小时均显示双相增加，峰值在4和24达因/cm 2，24小时水平高于0小时水平。MLO-Y 4细胞Ptgs 2表达类似地是双相的;然而，在流动后24小时，Ptgs 2 mRNA水平较低。我们的数据表明，2 T3和新生儿颅骨成骨细胞与MLO-Y 4骨细胞对PFVSS的反应机制的敏感性和动力学存在显着差异。此外，我们的数据支持PGE 2在介导响应于流体流动剪切应力的β-连环蛋白信号传导的激活中的作用。
The osteocyte is hypothesized to be the mechanosensory cell in bone. However, osteoblastic cell models have been most commonly used to investigate mechanisms of mechanosensation in bone. Therefore, we sought to determine if differences might exist between osteocytic and osteoblastic cell models relative to the activation of β-catenin signaling in MLO-Y4 osteocytic, 2T3 osteoblastic and primary neonatal calvarial cells (NCCs) in response to pulsatile fluid flow shear stress (PFFSS). β–catenin nuclear translocation was observed in MLO-Y4 cells at 2 and 16 dynes/cm2 PFFSS, but only at 16 dynes/cm2 in the 2T3 or NCC cultures. MLO-Y4 cells released high amounts of PGE2 into the media at all levels of PFFSS (2–24 dynes/cm2) and we observed a biphasic pattern of relative to the level of PFFSS. In contrast PGE2 release by 2T3 cells was only detected during 16 and 24 dynes/cm2 PFFSS starting at >1 hour and never reached the levels produced by MLO-Y4 cells. Exogenously added PGE2 was able to induce β–catenin nuclear translocation in all cells suggesting that the differences between the cell lines observed for β–catenin nuclear translocation was associated with the differences in PGE2 production. To investigate a possible mechanism for the differences in PGE2 release by MLO-Y4 and 2T3 cells we examined the regulation of Ptgs2 (Cox-2) gene expression by PFFSS. 2T3 cell Ptgs2 mRNA levels at both 0 and 24 hours after 2 hours of PFFSS showed biphasic increases with peaks at 4 and 24 dynes/cm2 and 24 hour levels were higher than 0 hour levels. MLO-Y4 cell Ptgs2 expression was similarly biphasic; however at 24 hours post flow Ptgs2 mRNA levels were lower. Our data suggest significant differences in the sensitivity and kinetics of the response mechanisms of 2T3 and neonatal calvarial osteoblastic versus MLO-Y4 osteocytic cells to PFFSS. Furthermore our data support a role for PGE2 in mediating the activation of β–catenin signaling in response to fluid flow shear stress.
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影响因子：
4.8
作者：
KLEINNULEND, J;VANDERPLAS, A;BURGER, EH
通讯作者：
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影响因子：
3.3
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