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通过MEK/ERK信号通路在磁性锌铁氧体涂层上实现磁场辅助细胞成骨分化

Magnetic-Field-Assisted Cellular Osteogenic Differentiation on Magnetic Zinc Ferrite Coatings via MEK/ERK Signaling Pathways.

作者信息

Tang Bolin, Shen Xiaojun, Ye Guanchen, Yang Yaru, Jiang Yang, Xia Hongqin, Chen Xiaoyi

机构信息

Key Laboratory of Yarn Materials Forming and Composite Processing Technology of Zhejiang Province, Jiaxing University, Jiaxing 314001, China.

The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

ACS Biomater Sci Eng. 2020 Dec 14;6(12):6864-6873. doi: 10.1021/acsbiomaterials.0c01087. Epub 2020 Nov 9.

DOI:10.1021/acsbiomaterials.0c01087
PMID:33320603
Abstract

Combining an external stimulus and stimuli-responsive biomaterials can regulate cellular behaviors. In this paper, a magneto-responsive zinc ferrite (ZnFeO) coating was designed to gain insight into the preosteoblasts behaviors and osteogenic differentiation mechanism under a static magnetic field (SMF). ZnFeO coatings with distinct magnetization (low, medium, and high magnetizations) were prepared by being annealed at different temperatures. Cellular biology experiments indicated that all ZnFeO coatings with the assistance of SMF could promote the early proliferation (3 days) and osteogenic differentiation of MC3T3-E1 cells. Among different ZnFeO samples, low and medium magnetization of ZnFeO showed a higher osteogenesis-related gene expression (Runx2, Col-I, OCN) than that of high magnetization ZnFeO under SMF, while cellular adhesion and proliferation cultured on different ZnFeO samples presented insignificant differences. Molecular biology tests showed that the combination of ferromagnetic ZnFeO and SMF could significantly improve the expression level of α2β1 integrin and p-ERK. However, the addition of the inhibitor U0126 sharply reduced the expression level of p-ERK, which indicated that α2β1 integrin-mediated MEK/ERK signaling pathways play a key role in SMF-assisted cellular osteogenic differentiation over ZnFeO coatings. This work provides an attractive strategy to enhance cellular osteogenic differentiation in a remote-control way, which exhibited enormous potential in the field of bone tissue repair and regeneration.

摘要

结合外部刺激和刺激响应性生物材料可以调节细胞行为。在本文中,设计了一种磁响应性铁酸锌(ZnFeO)涂层,以深入了解静态磁场(SMF)下前成骨细胞的行为和成骨分化机制。通过在不同温度下退火制备了具有不同磁化强度(低、中、高磁化强度)的ZnFeO涂层。细胞生物学实验表明,所有ZnFeO涂层在SMF的辅助下均可促进MC3T3-E1细胞的早期增殖(3天)和成骨分化。在不同的ZnFeO样品中,在SMF下,低磁化强度和中等磁化强度的ZnFeO比高磁化强度的ZnFeO表现出更高的成骨相关基因表达(Runx2、Col-I、OCN),而在不同ZnFeO样品上培养的细胞粘附和增殖没有显著差异。分子生物学测试表明,铁磁性ZnFeO和SMF的组合可显著提高α2β1整合素和p-ERK的表达水平。然而,添加抑制剂U0126会显著降低p-ERK的表达水平,这表明α2β1整合素介导的MEK/ERK信号通路在ZnFeO涂层的SMF辅助细胞成骨分化中起关键作用。这项工作提供了一种有吸引力的策略,以远程控制的方式增强细胞成骨分化,在骨组织修复和再生领域具有巨大潜力。

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