Int J Mol Sci:ZNF521抑制人脂肪来源干细胞中的成骨细胞分化

2019-01-13 MedSci MedSci原创

人脂肪来源的干细胞(hADSCs)是多能的间充质细胞,可分化成脂肪细胞,软骨细胞和骨细胞。在成骨细胞生成期间,骨祖细胞分化成成熟的成骨细胞并合成骨基质成分。锌指蛋白521(ZNF521/Zfp521)是涉及造血,神经和间充质干细胞调节的转录辅因子,其中已显示其抑制脂肪形成分化。本研究旨在确定ZNF521对hADSCs成骨细胞分化的影响,以阐明它是否可以影响其成骨转化。通过慢病毒载体转导实现了hAD

人脂肪来源的干细胞(hADSCs)是多能的间充质细胞,可分化成脂肪细胞,软骨细胞和骨细胞。在成骨细胞生成期间,骨祖细胞分化成成熟的成骨细胞并合成骨基质成分。锌指蛋白521(ZNF521/Zfp521)是涉及造血,神经和间充质干细胞调节的转录辅因子,其中已显示其抑制脂肪形成分化。本研究旨在确定ZNF521对hADSCs成骨细胞分化的影响,以阐明它是否可以影响其成骨转化。

通过慢病毒载体转导实现了hADSCs中ZNF521的强制表达或沉默。将细胞在商业成骨培养基中培养20天。通过形态学和分子标准评估,发现ZNF521强制表达显著降低了成骨细胞的发育,导致胶原蛋白I,碱性磷酸酶,osterix,骨桥蛋白和钙沉积物的水平降低。相反,ZNF521沉默,响应成骨细胞刺激,诱导成骨早期分子标志物的显着增加,并在后期阶段,显著增强基质矿化。

综上所述,这些结果表明ZNF521抑制hADSCs中的脂肪细胞和成骨细胞成熟,并表明其表达可能有助于维持hADSCs的不成熟特性。

原始出处:

Emanuela Chiarella, Annamaria Aloisio, et al., ZNF521 Represses Osteoblastic Differentiation in Human Adipose-Derived Stem Cells. Int J Mol Sci. 2018 Dec; 19(12): 4095.

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