Nanotopography on titanium promotes osteogenesis via autophagy-mediated signaling between YAP and β-catenin
Nanotopography on titanium promotes osteogenesis via autophagy-mediated signaling between YAP and β-catenin
复制标题
钛上的纳米形貌通过 YAP 和 β-catenin 之间自噬介导的信号促进成骨
DOI：
10.1016/j.actbio.2019.07.007
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发表时间：
2019-09-15
影响因子：
9.7
通讯作者：
Song, Jinlin
中科院分区：
文献类型：
--
作者：
Li, Lingjie;Yang, Sheng;Song, Jinlin
纳米结构钛植入物被认为是诱导成骨，但与地形相关的细胞信号转导尚未完全了解。植入物形貌与细胞核中β-连环蛋白指导的成骨转录因子的功能和细胞质中的自噬通量相关;雅普（Yes相关蛋白）与细胞质中β-连环蛋白的破坏有关，并且易受自噬通量影响。本研究调查了钛植入物的表面形貌是否调节细胞质雅普的自噬-溶酶体降解。钛表面改性光滑，微米，或纳米形貌。与光滑和微表面相比，纳米形貌与较高的β-连环蛋白核转位、成骨分化和自噬以及较少的胞质雅普相关。自噬-溶酶体途径的阻断导致雅普在MC 3 T3-E1细胞中的保留。胞质雅普限制性β-连环蛋白核转位。在纳米表面组中，β-连环蛋白在细胞核中的积累和成骨基因的表达得到改善。然而，在细胞-细胞（汇合）接触的情况下，与地形诱导的自噬相关的雅普和β-连环蛋白定位的操纵丢失。总之，观察到的具有纳米形貌的钛植入物的成骨反应涉及雅普和β-catenin.Statement的信号联系显著性具有粗糙形貌表面的钛广泛应用于骨科和牙科诊所。然而，促进骨生成的细胞对地形的反应和潜在机制尚未完全了解。在这项研究中，我们修改钛表面产生光滑，微米或纳米形貌。实验表明，纳米形貌诱导更强的自噬反应，导致降解的细胞质雅普。随着雅普水平的降低，β-catenin在细胞核中转运和积累，激活TCF/LEF转录因子，导致更强的成骨作用。此外，细胞-细胞接触在自噬介导的雅普和β-连环蛋白之间的信号联系中是必不可少的。因此，我们的研究揭示了一种新的信号转导纳米地形调控的骨生成，并支持生物材料表面的改性，以最大限度地提高骨整合。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Nanostructured titanium implants are recognized for inducing osteogenesis, but the cell signal transductions related to topography are not fully understood. Implant topography is associated with the functionality of osteogenic transcription factors directed by beta-catenin in the nucleus, and autophagic flux in the cytoplasm; YAP (Yes-associated protein) is implicated in the destruction of beta-catenin in the cytoplasm and is susceptible to autophagic flux. This study investigated whether surface topography of the titanium implant modulates autophagy-lysosome degradation of cytoplasmic YAP. Titanium surfaces were modified with smooth, micro, or nanotopographies. Compared with the smooth and micro surfaces, nanotopography was associated with higher beta-catenin nuclear translocation, osteogenic differentiation, and autophagy, and less cytoplasmic YAP. Blockade of the autophagy-lysosome pathway resulted in YAP retention in MC3T3-E1 cells. Cytoplasmic YAP restricted beta-catenin nuclear translocation. In the nano surface group, beta-catenin accumulation in the nucleus and expression of osteogenesis genes was improved. However, in the absence of cell-cell (confluent) contact, manipulation of YAP and beta-catenin localization associated with topography-induced autophagy was lost. In summary, the osteogenesis observed in response to titanium implants with nanotopography involves a signaling link between YAP and beta-catenin.Statement of SignificanceTitanium with rough topographical surfaces is extensively applied in orthopedic and dental clinics. However, the cellular response to topographies that promotes osteogenesis and underlying mechanisms are not fully understood. In this study, we modified titanium surfaces to produce smooth, micro, or nano topographies. Experiments indicated that the nanotopography induced a stronger autophagic response, leading to degraded cytoplasmic YAP. With the lower levels of YAP, beta-catenin transported and accumulated in the nucleus to activate TCF/LEF transcription factors, resulting in stronger osteogenesis. Additionally, cell-cell contact was essential in the autophagy-mediated signaling link between YAP and beta-catenin. Consequently, our investigation revealed a novel signal transduction in nanotopography-regulated osteogenesis, and supports the modification of biomaterial surfaces to maximize osseointegration. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.