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FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy.
Human Cell ( IF 4.3 ) Pub Date : 2020-09-13 , DOI: 10.1007/s13577-020-00421-y
Cheng Long 1 , Shiqiang Cen 1 , Zhou Zhong 1 , Chang Zhou 1 , Gang Zhong 1
Affiliation  

Mesenchymal stem cells (MSCs) are a promising regenerative medicine. The roles of miRNAs in osteogenic differentiation of bone marrow MSCs (BM-MSCs) remained less reported. Forkhead Box O3 (FOXO3) and alkaline phosphatase (ALP) levels in the BM-MSCs were measured on 3, 7, and 14 days after osteogenic differentiation. After transfection of FOXO3 overexpression plasmids or siFOXO3 into BM-MSCs, factors related to osteogenic differentiation or cell autophagy were determined. Besides, 3-methyladenine or rapamycin, as well as miR-223-3p mimic or inhibitor were applied to further determine the effect of FOXO3 in BM-MSCs. FOXO3 and ALP levels were increased in a time-dependent manner with osteogenic differentiation, supported by Alizarin Red Staining. Furthermore, up-regulated FOXO3 increased levels of ALP and factors related to osteogenic differentiation by increasing levels of autophagy-related factors. FOXO3, targeted by miR-223-3p, reversed the effects of miR-223-3p on factors related to BM-MSC autophagy and osteogenic differentiation. Down-regulated miR-223-3p expression promoted osteogenic differentiation of BM-MSCs by enhancing autophagy via targeting FOXO3, suggesting the potential of miR-223-3p as a therapeutic target for enhancing bone functions.



中文翻译:

FOXO3 被 miR-223-3p 靶向,通过增强自噬促进骨髓间充质干细胞的成骨分化。

间充质干细胞(MSCs)是一种很有前途的再生医学。miRNA在骨髓间充质干细胞(BM-MSCs)成骨分化中的作用仍然较少报道。在成骨分化后 3、7 和 14 天测量 BM-MSC 中的 Forkhead Box O3 (FOXO3) 和碱性磷酸酶 (ALP) 水平。在将 FOXO3 过表达质粒或 siFOXO3 转染到 BM-MSCs 后,确定了与成骨分化或细胞自噬相关的因素。此外,应用 3-甲基腺嘌呤或雷帕霉素以及 miR-223-3p 模拟物或抑制剂进一步确定 FOXO3 在 BM-MSCs 中的作用。在茜素红染色的支持下,FOXO3 和 ALP 水平随成骨分化呈时间依赖性增加。此外,上调 FOXO3 通过增加自噬相关因子的水平来增加 ALP 和与成骨分化相关的因子的水平。由 miR-223-3p 靶向的 FOXO3 逆转了 miR-223-3p 对 BM-MSC 自噬和成骨分化相关因子的影响。下调的 miR-223-3p 表达通过靶向 FOXO3 增强自噬促进 BM-MSCs 的成骨分化,表明 miR-223-3p 作为增强骨功能的治疗靶点的潜力。

更新日期:2020-09-13
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