Reversine Enhances Generation of Progenitor-like Cells by Dedifferentiation of Annulus Fibrosus Cells
Reversine Enhances Generation of Progenitor-like Cells by Dedifferentiation of Annulus Fibrosus Cells
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DOI：
10.1089/ten.tea.2009.0343
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发表时间：
2010-04-01
影响因子：
4.1
通讯作者：
Risbud, Makarand V.
中科院分区：
文献类型：
--
作者：
Saraiya, Mansi;Nasser, Rena;Risbud, Makarand V.
本研究的目的是确定用逆转碱（一种嘌呤类似物）治疗是否促进谱系定型纤维环细胞生成骨骼祖细胞。逆素调节纤维环细胞的细胞生长、形态和肌动蛋白细胞骨架。微阵列分析与 Ingenuity 通路分析相结合表明，逆向碱处理导致许多基因发生显着的表达变化，包括细胞与细胞相互作用、细胞运动、细胞生长和发育所需的基因。进一步的分析表明，与细胞组装和组织、DNA 复制和修复、组织形态和细胞间信号传导有关的基因网络参与其中。基因表达谱取决于逆氨酸浓度。在成骨培养基中，用 300nM reversine 预处理的细胞表现出碱性磷酸酶活性的诱导增加以及碱性磷酸酶、骨唾液蛋白、骨钙素和 I 型胶原蛋白 mRNA 表达的增强。维持在脂肪形成培养基中，经逆向素预处理的环状细胞显示出脂肪形成分化的证据：胞质脂滴的积累以及PPAR-γ 2、LPL和Fabp mRNA的表达增加。在软骨形成培养基中，用逆转素预处理的细胞表现出聚集蛋白聚糖、II、IX和XI型胶原蛋白以及多功能蛋白聚糖的诱导显着增加。结论是，逆向素处理诱导纤维环细胞可塑性并促进其沿间充质谱系分化。该试剂可用于生成骨骼祖细胞以协调椎间盘的修复。
The aim of this study was to determine if treatment with reversine, a purine analog, promoted generation of skeletal progenitor cells from lineage-committed annulus fibrosus cells. Reversine modulated cell growth, morphology, and the actin cytoskeleton of annulus fibrosus cells. Microarray profiling coupled with Ingenuity Pathway Analysis revealed that reversine treatment resulted in a significant expression change in many genes including those required for cell-cell interaction, cell movement, cell growth, and development. Further analysis revealed that there was involvement of gene networks concerned with cellular assembly and organization, DNA replication and repair, tissue morphology, and cell-to-cell signaling. The gene expression profile was dependent on reversine concentration. In osteogenic media, cells pretreated with 300nM reversine exhibited an increased induction in alkaline phosphatase activity and enhanced expression of alkaline phosphatase, bone sialoprotein, osteocalcin, and collagen type I mRNA. Maintained in adipogenic media, the reversine-pretreated annulus cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of PPAR-gamma 2, LPL, and Fabp mRNA. In chondrogenic media, cells pretreated with reversine exhibited marked increase in the induction of aggrecan, collagen types II, IX, and XI, and versican. It is concluded that reversine treatment induced annulus fibrosus cell plasticity and promoted their differentiation along mesenchymal lineages. This agent could be used to generate skeletal progenitor cells to orchestrate the repair of the intervertebral disc.