α10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential
α10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential
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DOI：
10.1089/scd.2007.0049
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Kjellman, Christian
中科院分区：
文献类型：
--
作者：
Varas, Laura;Ohlsson, Lars Bryngelson;Kjellman, Christian
间充质干细胞（MSC）是具有分化成各种不同细胞谱系的能力的多能细胞，并且可以生成骨、软骨和脂肪组织。目前使用广泛的不同细胞表面标志物表征MSC，所述细胞表面标志物不是MSC独有的并且对培养条件或分化能力不敏感。我们表明，整合素亚基α 10和所有的胶原结合整合素α 10 β 1和α 11 β 1表达的人MSC在单层培养。我们还表明，在软骨形成培养基中的MSC聚集培养期间，α 10的表达增加，而α 10 β 1和所有减少。α 10 β 1由软骨中的软骨细胞表达，而α 11 β 1整联蛋白主要由成纤维细胞谱系的亚群表达。在广泛的MSC单层培养中，α 10表达下调。我们发现，这种下调是逆转成纤维细胞生长因子-2（FGF-2）的治疗。向MSC中添加FGF-2不仅导致α 10表达增加，而且还导致所有表达降低。FGF-2处理MSC已显示出保持细胞更具多能性，并且还诱导细胞增殖和Sox-9上调。我们证明了具有高α 10表达的FGF-2处理的MSC的软骨形成能力的改善以及胶原依赖性迁移潜力的增加。我们还证明了α 10和所有整合素亚基在小鼠的骨内膜和骨膜中的表达，但在新鲜抽吸的人或小鼠BM中的表达水平非常低或不可检测。我们发现，具有高软骨分化潜力的MSC是高度α 10阳性，并提出α 10作为一个潜在的标志物来预测MSC的分化状态。
Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to differentiate into various different cell lineages and can generate bone, cartilage and adipose tissue. MSCs are presently characterized using a broad range of different cell-surface markers that are not exclusive to MSCs and not sensitive to culture conditions or differentiation capacity. We show that the integrin subunits alpha 10 and all of the collagen binding integrins alpha 10 beta 1 and alpha 11 beta 1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of alpha 10 increases, while alpha 10 beta 1 and all decrease, during aggregate culture of MSCs in chondrogenic medium. alpha 10 beta 1 is expressed by chondrocytes in cartilage, whereas alpha 11 beta 1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, alpha 10 expression is down-regulated. We show that this down-regulation is reversed by fibroblast growth factor-2 (FGF-2) treatment. Addition of FGF-2 to MSCs not only results in increased alpha 10 expression, but also in decreased all expression. FGF-2 treatment of MSCs has been shown to keep the cells more multipotent and also induces cell proliferation and Sox-9 up-regulation. We demonstrate improved chondrogenecity as well as increased collagen-dependant migratory potential of FGF-2-treated MSCs having a high alpha 10 expression. We also demonstrate expression of alpha 10 and all integrin subunits in the endosteum and periosteum of mice, but very low or not detectable expression levels in freshly aspired human or mouse BM. We show that MSCs with high chondrogenic differentiation potential are highly alpha 10 positive and propose alpha 10 as a potential marker to predict the differentiation state of MSCs.