ROCK-TAZ signaling axis regulates mechanical tension-induced osteogenic differentiation of rat cranial sagittal suture mesenchymal stem cells
ROCK-TAZ signaling axis regulates mechanical tension-induced osteogenic differentiation of rat cranial sagittal suture mesenchymal stem cells
复制标题
ROCK-TAZ信号轴调节机械张力诱导的大鼠颅矢状缝间充质干细胞成骨分化
DOI：
10.1002/jcp.29522
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发表时间：
2020-01-22
影响因子：
5.6
通讯作者：
Zhang, Wei-Bing
中科院分区：
文献类型：
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作者：
Li, Wenlei;Zhao, Jing;Zhang, Wei-Bing
穿过缝线的机械力能够促进缝线成骨。正畸诊所经常使用缝线的这种生物学特性来治疗先天性颅颌面畸形。然而，对潜在的机制仍然知之甚少。颅面缝提供了一个特殊的生长源，并支持骨生成的主要部位。在这里，我们分离出大鼠矢状缝细胞（rSAGs），它具有间充质干细胞的特性和分化能力。然后使细胞经受机械张力（5%伸长，0.5Hz;正弦波形），这表明机械张力可以增强成骨分化，但几乎不影响rSAG的增殖。此外，机械张力可增加Rho相关激酶（ROCK）的表达，并增强转录辅激活因子与PDZ结合基序（TAZ）的核转位。抑制ROCK表达可以抑制张力诱导的骨生成，并阻断张力诱导的核TAZ上调。此外，我们的研究结果表明，TAZ与rSAGs中的Runx 2有直接的结合位点，并且无论有无机械张力，敲低的TAZ都同时降低Runx 2的表达。综上所述，我们的研究结果表明，rSAGs在体外的多能性可以引起机械张力下的早期成骨分化，这是由ROCK-TAZ信号轴介导的。
Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.