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Mechanisms of Cdc42-mediated rat MSC differentiation on micro/nano-textured topography

机译：CDC42介导的大鼠MSC分化对微/纳米纹理地形的机制

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摘要

Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/beta-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/beta-catenin is the underlying mechanism. To confirm the hypothesis, we first tested rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano-textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling activity. The results show that micro/nano-textured topography enhances MSCs' osteogenic differentiation. In addition, the cells' morphology and cytoskeletal reorganization were dramatically different on smooth surfaces and micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well as accumulation of beta-catenin in the nucleus, were up-regulated by micro/nano-textured topography. Cdc42 protein expression was markedly increased under these conditions; conversely, Cdc42 silencing significantly depressed the enhancement of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover, Cdc42si attenuated p-GSK3 beta activation and resulted in p-catenin cytoplasmic degradation on the micro/nano-textured topography. Our results indicate that Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization, and that crosstalk between Cdc42 and Wnt/beta-catenin signaling though GSK3p regulates MSCs osteogenic differentiation by implant topographical cues.
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  • 来源
    《Acta biomaterialia》 |2017年第2017期|共12页
  • 作者

    Li Guangwen; Song Yanyan; Shi Mengqi; Du Yuanhong; Wang Wei; Zhang Yumei;

  • 作者单位

    Fourth Mil Med Univ Sch Stomatol State Key Lab Mil Stomatol Xian 710032 Peoples R China;

    Xinjiang Med Univ Affiliated Hosp 1 Dept Prosthodont Xinjiang 830054 Peoples R China;

    Fourth Mil Med Univ Sch Stomatol State Key Lab Mil Stomatol Xian 710032 Peoples R China;

    PLA Dept Stomatol Hosp 463 Shenyang 110042 Peoples R China;

    PLA Dept Stomatol Hosp 463 Shenyang 110042 Peoples R China;

    Fourth Mil Med Univ Sch Stomatol State Key Lab Mil Stomatol Xian 710032 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

    Micro/nano-textured topography; MSC; Cdc42; Wnt/beta-catenin pathway;

    机译：微/纳米纹理地形;MSC;CDC42;WNT /β-连环蛋白途径;

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