Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells
Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells
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DOI：
10.1016/j.bbrc.2006.06.110
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发表时间：
2006-08-18
影响因子：
3.1
通讯作者：
Putnam, Andrew J.
中科院分区：
文献类型：
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作者：
Kundu, Anup K.;Putnam, Andrew J.
各种可溶性因子在促进成体间充质干细胞（mesenchymal stem cells，MSCs）向成骨细胞分化中的作用已被广泛研究，但细胞外基质（extracellular matrix，ECM）是如何指导MSCs从生长到分化的表型转变的，目前尚不清楚。为了研究这个问题，我们培养的MSC纯化玻连蛋白或I型胶原蛋白，我们早期的组织工程工作的动机表明，MSC粘附到聚合物支架主要是由被动吸附这两个ECM配体从血清介导的。使用碱性磷酸酶活性和基质矿化成骨的早期和晚期阶段，分别作为指标，我们在这里报告，这两个基板支持分化，但机制是基板依赖性。具体而言，玻连蛋白上的成骨与增强的粘着斑形成、粘着斑激酶（FAK）和桩蛋白的活化相关。以及细胞外信号调节激酶（ERK）和磷脂酰肌醇-3激酶（PI 3 K）途径的活化减弱。相比之下，I型胶原上的MSC表现出减少的粘着斑形成，减少的FAK和桩蛋白的活化，以及增加的ERK和PI 3 K的活化。ERK和FAK的抑制阻断了两种底物上的矿物质沉积，这表明所观察到的信号传导途径的差异最终收敛于相同的细胞命运。了解这些机制差异对于可预测地控制MSC的成骨分化并扩大其在再生医学中的应用至关重要。(c)2006年爱思唯尔公司All rights reserved.
The roles of various soluble factors in promoting the osteogenic differentiation of adult mesenchymal stem cells (MSCs) have been widely studied, but little is known about how the extracellular matrix (ECM) instructs the phenotypic transition between growth and differentiation. To investigate this question, we cultured MSCs on purified vitronectin or type-I collagen, motivated by our earlier tissue engineering work demonstrating that MSC adhesion to polymer scaffolds is primarily mediated by the passive adsorption of these two ECM ligands from serum. Using alkaline phosphatase activity and matrix mineralization as indicators of the early and late stages of osteogenesis, respectively, we report here that both substrates supported differentiation, but the mechanism was substrate dependent. Specifically, osteogenesis on vitronectin correlated with enhanced focal adhesion formation, the activation of focal adhesion kinase (FAK) and paxillin.. and the diminished activation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 kinase (PI3K) pathways. By contrast, MSCs on type-I collagen exhibited reduced focal adhesion formation, reduced activation of FAK and paxillin, and increased activation of ERK and PI3K. Inhibition of ERK and FAK blocked mineral deposition on both substrates, suggesting that the observed differences in signaling pathways ultimately converge to the same cell fate. Understanding these mechanistic differences is essential to predictably control the osteogenic differentiation of MSCs and widen their use in regenerative medicine. (c) 2006 Elsevier Inc. All rights reserved.