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首页> 外文期刊>Journal of Cellular Physiology >Regulating osteogenesis and adipogenesis in adipose‐derived stem cells by controlling underlying substrate stiffness
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Regulating osteogenesis and adipogenesis in adipose‐derived stem cells by controlling underlying substrate stiffness

机译：调节骨生成和脂肪生成通过控制脂肪量推导出干细胞底层基板刚度

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摘要

Cells reside in a complex microenvironment (niche) in which the biochemical and biophysical properties of the extracellular matrix profoundly affect cell behavior. Extracellular stiffness, one important bio‐mechanical characteristic of the cell niche, is important in regulating cell proliferation, migration, and lineage specification. However, the mechanism by which mechanical signals guide osteogenic and adipogenic commitment of stem cells remains difficult to dissect. To explore this question, we generated a range of polydimethylsiloxane‐based matrices with differing degrees of stiffness that mimicked the stiffness seen in natural tissues and examined adipose stem cell morphology, spreading, vinculin expression, and differentiation along the osteogenic and adipogenic pathways. Rigid matrices allowed broader cell spreading, faster growth rate and stronger expression of vinculin in adipose‐derived stem cells. In the presence of inductive culture media, stiffness‐dependent osteogenesis and adipogenesis of the adipose stem cells indicated that there was a combinatorial effect of biophysical and biochemical cues; no such lineage specification was observed in normal media. Osteogenic differentiation behavior showed a correlation with matrix rigidity, as well as with elevated expression of RhoA, ROCK‐1/‐2, and related proteins in the Wnt/β‐catenin pathway. The result provides a comprehensive understanding of how stem cells respond to the surrounding microenvironment and points to the fact that matrix stiffness is a critical element in biomaterial design and this will be an important advance in stem cell‐based tissue engineering.
机译：细胞存在于一个复杂的微环境(利基)生物化学和生物物理细胞外基质深刻的属性影响细胞行为。一个重要的生物力学特征细胞的利基,在调节细胞是很重要的增殖、迁移和血统规范。机械信号引导成骨的和干细胞脂肪形成的承诺仍然存在难以解剖。我们生成一系列基于聚二甲硅氧烷量矩阵不同程度的刚度,模仿刚度在自然的组织和检查脂肪干细胞形态、传播、vinculin表情,和分化成骨、脂肪形成的途径。矩阵允许更广泛的细胞传播,速度更快vinculin的生长速度和更强的表达在脂肪量推导出干细胞。归纳文化传媒、刚度的依赖骨生成和脂肪形成的脂肪干细胞细胞表明组合生物物理和生物化学信号的影响;这样的血统规范中观察到正常媒体。关联矩阵和刚度,以及RhoA表达升高,岩石量1 /高2相关的蛋白质在Wnt /β连环蛋白通路。结果提供了一个全面的了解干细胞如何应对周围微环境,指出了这一事实刚度矩阵是一个至关重要的元素生物材料的设计,这将是一个重要的提前进入干细胞组织工程。

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