Hyaluronan-based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of CD44 and CD54
Hyaluronan-based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of CD44 and CD54
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DOI：
10.1002/jcp.20572
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发表时间：
2006-05-01
影响因子：
5.6
通讯作者：
Facchini, A
中科院分区：
文献类型：
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作者：
Lisignoli, G;Cristino, S;Facchini, A
透明质酸（HA）是骨髓基质中细胞外基质（ECM）的主要非蛋白糖胺聚糖成分，参与细胞定位、增殖、分化以及受体介导的基因表达变化。骨修复和骨髓再生依赖于细胞外基质、趋化因子等炎症因子以及金属蛋白酶等降解因子。我们在体外分析了人间充质干细胞（h - MSCs）与一种基于透明质酸的三维（3 - D）支架之间的相互作用。通过实时定量聚合酶链反应（Real - time PCR）、酶联免疫吸附测定（ELISA）和免疫细胞化学技术，对在塑料培养皿或基于透明质酸的支架上培养的h - MSCs中CXC趋化因子/受体（CXCL8（白细胞介素 - 8）/CXCR1 - 2、CXCL10（干扰素诱导蛋白 - 10）/CXCR3、CXCL12（基质细胞衍生因子 - 1）/CXCR4和CXCL13（B细胞趋化因子 - 1）/CXCR5）以及金属蛋白酶/抑制剂（MMP - 1、MMP - 3、MMP - 13/组织金属蛋白酶抑制剂 - 1（TIMP - 1））的表达进行了评估。此外，还分析了两种透明质酸受体CD44和CD54的表达。我们在mRNA和蛋白质水平上均发现，基于透明质酸的支架诱导了CXCR4、CXCL13和MMP - 3的表达，并下调了CXCL12、CXCR5、MMP - 13和TIMP - 1的表达，而基于透明质酸的支架诱导了CD54的表达，但未诱导CD44的表达。我们发现这两种透明质酸受体直接参与了对CXCL12、CXCL13和CXCR5的调节。这项研究表明，一种广泛用于软骨和骨修复的基于透明质酸的三维支架，在调节人间充质干细胞的炎症因子和降解因子方面具有直接作用，这些因子直接参与特定细胞类型在受损区域的植入。我们的数据清楚地表明，这种三维构象的透明质酸对人间充质干细胞起到信号分子的作用。《细胞生理学杂志》2006年第207卷第364 - 373页。（c）2005威利 - 利斯公司
Hyaluronan (HA), in the bone marrow stroma, is the major non-protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor-mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h-MSCs) and a three-dimensional (3-D) HA-based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL-8)/CXCR1-2, CXCL10 (IP-10)/CXCR3, CXCL12 (SDF-1)/CXCR4, and CXCL13 (BCA-1)/CXCR5, and metalloproteinases/inhibitors MMP-1, MMP-3, MMP-13/TIMP-1 were evaluated in h-MSCs grown on plastic or on HA-based scaffold by Real-time PCR, ELISA, and immunocytochernical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA-based scaffold induced the expression of CXCR4, CXCL13, and MMP-3 and downmodulated the expression of CXCL12, CXCR5, MMP-1 3, and TIMP-1 while HA-based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCLI 2, CXCL13, and CXCR5. This study demonstrates a direct action of a 3-D HA-based scaffold, widely used for cartilage and bone repair, in modulating both h-MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3-D conformation acts as a signaling molecule for h-MSCs. J. Cell. Physiol. 207: 364-373, 2006. (c) 2005 Wiley-Liss, Inc.