Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells through down regulating the transcriptional co-activator TAZ
Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells through down regulating the transcriptional co-activator TAZ
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DOI：
10.1016/j.bbrc.2015.11.006
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发表时间：
2015-12-04
影响因子：
3.1
通讯作者：
Song, Guanbin
中科院分区：
文献类型：
--
作者：
Chen, Zhe;Luo, Qing;Song, Guanbin
在空间飞行或模拟实验中，微重力可引起骨丢失，但其机制尚不清楚。本文利用回转器模拟微重力，发现微重力对大鼠骨髓间充质干细胞成骨分化有明显的抑制作用。我们检测到SMG显着抑制具有PDZ结合基序（TAZ）的转录辅激活因子的表达，TAZ是骨生成的重要调节因子。有趣的是，我们发现溶血磷脂酸（LPA）可以激活TAZ并保持SMG下BMSCs的成骨分化。我们的数据进一步表明，通过siRNA消耗TAZ阻断了SMG下LPA诱导的BMSCs成骨分化的增加。此外，Y27632（Rock抑制剂）取消了TAZ的激活和LPA诱导的成骨分化的增加。综上所述，我们认为微重力可通过降低TAZ表达抑制BMSCs的成骨分化，而LPA可通过Rock-TAZ途径有效逆转成骨分化的降低。(C)2015爱思唯尔公司All rights reserved.
Microgravity induces observed bone loss in space flight or simulated experiments, while the mechanism underlying it is still obscure. Here, we utilized a clinostat to model simulated microgravity (SMG) and found that SMG obviously inhibited osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). We detected that SMG dramatically inhibited the expression of the transcriptional coactivator with PDZ-binding motif (TAZ), which acts as a vital regulator of osteogenesis. Interestingly, we found that lysophosphatidic acid (LPA) could activate TAZ and retain osteogenic differentiation of BMSCs under SMG. Our data further demonstrated that depletion of TAZ by siRNA blocked the LPA-induced increase in osteogenic differentiation of BMSCs under SMG. Moreover, Y27632 (the Rock inhibitor) abrogated the activation of TAZ and the increased osteogenic differentiation induced by LPA. Taken together, we propose that microgravity inhibits osteogenic differentiation of BMSCs due to decreased TAZ expression and that LPA can efficiently reverse the reduced osteogenic differentiation via the Rock-TAZ pathway. (C) 2015 Elsevier Inc. All rights reserved.