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Research Article

3 -氨基丁酸通过诱导TNFAIP3促进间充质干细胞的成骨分化

卷 20, 期 2, 2020

页: [152 - 161] 页: 10

弟呕挨: 10.2174/1566523220999200727122502

价格: $65

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摘要

背景：骨质疏松症是最常见的代谢性骨骼疾病。对于像骨质疏松症治疗一样有益的新型治疗药物的需求仍然没有得到满足。有报道称，神经递质-氨基丁酸(GABA)可能与人骨形成有关。然而，确切的机制仍不清楚。 目的：探讨GABA对骨代谢的影响，并探讨TNFAIP3在这一过程中的可能作用。 方法：细胞计数kit-8 (CCK-8)实验表明，GABA对人间充质干细胞(hMSCs)和RAW 264.7细胞增殖的影响不大。实验结果表明，GABA增强了成骨诱导过程中hMSCs的ALP染色强度、ALP活性和Ca2+矿化结节的积累。 结果：qRT-PCR结果显示GABA处理显著提高了hMSCs成骨基因的mRNA表达。在RAW 264.7细胞中，TRAP染色显示GABA没有改变破骨细胞的数量和大小，也没有改变破骨细胞基因的表达，显示GABA不影响破骨细胞分化。机制上，GABA治疗显著诱导TNFAIP3的持续表达。此外，通过敲除TNFAIP3，拮抗GABA的成骨作用，提示TNFAIP3介导GABA在hMSCs中的作用。 结论：我们的结果显示GABA通过上调TNFAIP3正向调节成骨分化，而对破骨细胞分化无明显影响。因此，我们的研究结果为骨质疏松症和低骨密度的治疗提供了一种潜在的基因疗法。

关键词: GABA，骨质疏松，成骨细胞，破骨细胞，MSCs

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