Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics
Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics
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DOI：
10.1007/s12079-017-0425-3
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发表时间：
2018-03
影响因子：
4.1
通讯作者：
Tadashi Yamamoto;Yuki Ugawa;M. Kawamura;K. Yamashiro;Shinsuke Kochi;Hidetaka Ideguchi;S. Takashiba
中科院分区：
文献类型：
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作者：
Tadashi Yamamoto;Yuki Ugawa;M. Kawamura;K. Yamashiro;Shinsuke Kochi;Hidetaka Ideguchi;S. Takashiba
当细胞感知其微环境的变化时，它们以各种方式表现;细胞的行为由它们与生长因子、小生境细胞和细胞外基质（ECM）的协调相互作用指导。微环境的调节影响细胞形态和多种基因表达。Rho/Rho相关的含有卷曲螺旋的蛋白激酶（ROCK）信号传导是细胞骨架动力学的关键调节因子之一，并且通过与微环境的相互通信主动和/或被动地决定细胞命运，例如增殖、迁移、分化和凋亡。在牙周创伤愈合过程中，将驻留干细胞募集到缺损部位对于牙周组织的再生和内环境稳定是重要的。牙周膜韧带（PDL）细胞含有异质成纤维细胞群，包括间充质干细胞，并有助于牙齿支持组织的重建。因此，牙周膜细胞的生物再生一直是牙周治疗的最终目标。最近的干细胞研究揭示了内在ECM特性，提供了细胞命运决定的范式转变。本文就ROCK活性及其特异性抑制剂Y-27632在ECM微环境调控中的作用作一综述。此外，它提出了目前的理解Rho/ROCK信号如何影响干细胞，特别是PDL细胞的命运决定。此外，我们还详细讨论了微环境相互反应背后的潜在机制。
Cells behave in a variety of ways when they perceive changes in their microenvironment; the behavior of cells is guided by their coordinated interactions with growth factors, niche cells, and extracellular matrix (ECM). Modulation of the microenvironment affects the cell morphology and multiple gene expressions. Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) signaling is one of the key regulators of cytoskeletal dynamics and actively and/or passively determines the cell fate, such as proliferation, migration, differentiation, and apoptosis, by reciprocal communication with the microenvironment. During periodontal wound healing, it is important to recruit the residential stem cells into the defect site for regeneration and homeostasis of the periodontal tissue. Periodontal ligament (PDL) cells contain a heterogeneous fibroblast population, including mesenchymal stem cells, and contribute to the reconstruction of tooth-supporting tissues. Therefore, bio-regeneration of PDL cells has been the ultimate goal of periodontal therapy for decades. Recent stem cell researches have shed light on intrinsic ECM properties, providing paradigm shifts in cell fate determination. This review focuses on the role of ROCK activity and the effects of Y-27632, a specific inhibitor of ROCK, in the modulation of ECM-microenvironment. Further, it presents the current understanding of how Rho/ROCK signaling affects the fate determination of stem cells, especially PDL cells. In addition, we have also discussed in detail the underlying mechanisms behind the reciprocal response to the microenvironment.