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首页> 外文期刊>Stem cells international >Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells
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Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells

机译:地塞米松调节Epha5,具有人骨髓基质细胞的成骨能力的潜在抑制因子

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摘要

We previously demonstrated the importance of quality management procedures for the handling of human bone marrow stromal cells (hBMSCs) and provided evidence for the existence of osteogenic inhibitor molecules in BMSCs. One candidate inhibitor is the ephrin type-A receptor 5 (EphA5), which is expressed in hBMSCs and upregulated during long-term culture. In this study, forced expression of EphA5 diminished the expression of osteoblast phenotypic markers. Downregulation of endogenous EphA5 by dexamethasone treatment promoted osteoblast marker expression. EphA5 could be involved in the normal growth regulation of BMSCs and could be a potential marker for replicative senescence. Although Eph forward signaling stimulated by ephrin-B-Fc promoted the expression of ALP mRNA in BMSCs, exogenous addition of EphA5-Fc did not affect the ALP level. The mechanism underlying the silencing of EphA5 in early cultures remains unclear. EphA5 promoter was barely methylated in hBMSCs while histone deacetylation could partially suppress EphA5 expression in early-passage cultures. In repeatedly passaged cultures, the upregulation of EphA5 independent of methylation could competitively inhibit osteogenic signal transduction pathways such as EphB forward signaling. Elucidation of the potential inhibitory function of EphA5 in hBMSCs may provide an alternative approach for lineage differentiation in cell therapy strategies and regenerative medicine.
机译:我们之前展示了质量管理程序处理人骨髓基质细胞(HBMSCs)的重要性,并提供了BMSCs中骨质发生抑制剂分子存在的证据。一个候选抑制剂是ephrin类型-a受体5(EphA5),其在HBMSCs中表达并在长期培养期间上调。在该研究中,Epha5的强迫表达降低了成骨细胞表型标志物的表达。地塞米松治疗的内源性EphA5的下调促进了成骨细胞标记表达。 Epha5可以参与BMSC的正常生长调节,并且可以是复制衰老的潜在标志物。虽然Ephrin-B-Fc刺激的Eph转发信号促进BMSC中ALP mRNA的表达,但外源添加Epha5-Fc并未影响ALP水平。早期培养物沉默的机制仍然尚不清楚。 EphA5启动子在HBMSC中几乎甲基化,而组蛋白脱乙酰化可以部分抑制早期培养物中的EphA5表达。在反复传代的培养物中,独立于甲基化的Epha5的上调可以竞争性地抑制ephb前向信号传导的成骨信号转导途径。阐明HBMSCS中EphA5的潜在抑制功能可以提供细胞治疗策略和再生医学中的谱系分化的替代方法。

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