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Mesenchymal stem cells-derived and siRNAs-encapsulated exosomes inhibit osteonecrosis of the femoral head.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-08-04 , DOI: 10.1111/jcmm.15395
Chi Zhang 1 , Yan Su 1 , Hao Ding 1 , Jimin Yin 1 , Zhenhong Zhu 1 , Wenqi Song 1
Affiliation  

Osteonecrosis of the femoral head (ONFH) is a progressive, obstinate and disabling disease. At present, the treatment of ONFH is still a global medical problem. We aim to explore the role of bone mesenchymal stem cells (BMSCs)‐derived and siRNAs‐encapsulated exosomes (siRNAs‐encapsulated BMSCexos) in ONFH. We first isolated BMSCexos and screened siRNAs of 6 ONFH‐related genes for siRNAs‐encapsulated BMSCexo. The expression of these 6 ONFH‐related genes in dexamethasone (DXM)‐treated MC3T3‐E1 cell, cell model of ONFH, was detected by RT‐qPCR and Western blot analysis. And then, we performed CCK‐8 assay, angiogenesis assay and HE staining analysis to test the promotion role of the siRNAs‐encapsulated BMSCexo for angiogenesis during ONFH repair. The results suggest that the obtained particles were BMSCexos. The screened effective siRNAs could effectively knock down their expression in VECs. Moreover, siRNAs‐encapsulated BMSCexo could effectively knock down the expression of these genes in VECs. In addition, siRNAs‐encapsulated BMSCexo promote angiogenesis during ONFH repair. In conclusion, we found siRNAs‐encapsulated BMSCexos could promote ONFH repair by angiogenesis, and indicated exosome as the new siRNA carrier is of great significance to improve the efficiency of RNAi.

中文翻译:

间充质干细胞来源和siRNA封装的外泌体抑制股骨头的骨坏死。

股骨头坏死(ONFH)是一种进行性,顽固性和致残性疾病。目前,ONFH的治疗仍然是全球性的医学问题。我们旨在探讨骨间充质干细胞(BMSCs)和siRNA封装的外泌体(siRNA封装的BMSCexos)在ONFH中的作用。我们首先分离了BMSCexos,并筛选了6个ONFH相关基因的siRNA,用于siRNA封装的BMSCexo。通过RT-qPCR和Western blot分析检测了地塞米松(DXM)处理的MC3T3-E1细胞(ONFH的细胞模型)中这6个ONFH相关基因的表达。然后,我们进行了CCK-8分析,血管生成分析和HE染色分析,以测试siRNA封装的BMSCexo在ONFH修复过程中对血管生成的促进作用。结果表明,获得的颗粒是BMSCexos。筛选出的有效siRNA可以有效敲低它们在VEC中的表达。此外,siRNA封装的BMSCexo可以有效敲低VEC中这些基因的表达。此外,siRNA封装的BMSCexo可以促进ONFH修复过程中的血管生成。总之,我们发现包裹有siRNA的BMSCexos可以通过血管生成促进ONFH修复,并表明外来体是新型siRNA载体,对于提高RNAi的效率具有重要意义。
更新日期:2020-09-28
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