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纳米拓扑板通过 TAZ 激活促进成骨分化。

Nanotopological plate stimulates osteogenic differentiation through TAZ activation.

机构信息

Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea.

Department of Interdisciplinary Bio/Micro System Technology, College of Engineering, Korea University, Seoul, 02841, Korea.

出版信息

Sci Rep. 2017 Jun 15;7(1):3632. doi: 10.1038/s41598-017-03815-5.

Abstract

The topographical environment, which mimics the stem cell niche, provides mechanical cues to regulate the differentiation of mesenchymal stem cells (MSC). Diverse topographical variations have been engineered to investigate cellular responses; however, the types of mechanical parameters that affect cells, and their underlying mechanisms remain largely unknown. In this study, we screened nanotopological pillars with size gradient to activate transcriptional coactivator with PDZ binding motif (TAZ), which stimulates osteogenesis of MSC. We observed that a nanotopological plate, 70 nm in diameter, significantly induces osteogenic differentiation with the activation of TAZ. TAZ activation via the nanotopological plate was mediated by actin polymerization and Rho signaling, as evidenced by the cytosolic localization of TAZ under F-actin or Rho kinase inhibitor. The FAK and MAPK pathways also play a role in TAZ activation by the nanotopological plate because the inhibitor of ERK and JNK blocked nanopattern plate induced osteogenic differentiation. Taken together, these results indicate that nanotopology regulates cell differentiation through TAZ activation.

摘要

地形环境模拟干细胞龛,提供机械线索来调节间充质干细胞(MSC)的分化。已经设计了多种地形变化来研究细胞反应;然而,影响细胞的机械参数类型及其潜在机制在很大程度上仍不清楚。在这项研究中,我们筛选了具有尺寸梯度的纳米拓扑柱来激活含有 PDZ 结合基序的转录共激活因子(TAZ),这刺激了 MSC 的成骨分化。我们观察到,直径为 70nm 的纳米拓扑板通过 TAZ 的激活显著诱导成骨分化。通过纳米拓扑板的 TAZ 激活是通过肌动蛋白聚合和 Rho 信号转导介导的,这可以通过 F-肌动蛋白或 Rho 激酶抑制剂下 TAZ 的细胞质定位来证明。FAK 和 MAPK 途径也在纳米拓扑板诱导的 TAZ 激活中发挥作用,因为 ERK 和 JNK 的抑制剂阻断了纳米图案板诱导的成骨分化。总之,这些结果表明,纳米拓扑结构通过 TAZ 的激活来调节细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e04e/5472602/b4d4d1a9d04e/41598_2017_3815_Fig1_HTML.jpg

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