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三七总皂苷 R1 通过 MAPK 和 JAK1/STAT3 通路上调 miR-23a 促进 MC3T3-E1 分化。

Notoginsenoside R1 promotes MC3T3-E1 differentiation by up-regulating miR-23a via MAPK and JAK1/STAT3 pathways.

机构信息

a Department of Hand and Foot Microsurgery , Dalian Municipal Central Hospital Affiliated of Dalian Medical University , Dalian , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):603-609. doi: 10.1080/21691401.2019.1573189.

DOI:10.1080/21691401.2019.1573189
PMID:30831034
Abstract

Growing evidence have probed a stimulatory influence of Notoginsenoside R1 (NGR1) with osteoblastic probability. miR-23a plays a crucial role in osteoblast differentiation. Whereas whether there exists a miRs-related mechanism by which NGR1 promotes preosteoblast differentiation remains unexplored. We pre-treated MC3T3-E1 with NGR1 to anatomize Runx-2 and Osx expression as well as ALP activity. Phosphorylation of regulators was evaluated by Western blot. SB203580 and Ruxolitinib were used to reduce the phosphorylation of regulators. The effects of NGR1 on miR-23a were verified by qRT-PCR. We analyzed the expression of Runx-2 and Osx, ALP activity as well as phosphorylation of regulators in MC3T3-E1 stimulated with NGR1 and transfected with miR-23a inhibitor. We found that NGR1 enhanced Runx-2 and Osx expression as well as ALP activity in a concentration-dependent manner. NGR1 might exhibit an efficacious promotion on Runx-2, Osx and ALP activity by increased phosphorylation of MAPK, JAK1, and STAT3. NGR1 resulted in miR-23a overexpression which positively modulated Runx-2 and Osx expression as well as ALP activity. Our results showed that miR-23a inhibitor reduced the phosphorylation of MAPK, JAK1 and STAT3 in MC3T3-E1 pre-treated with NGR1. In conclusion, NGR1 exhibited an efficacious promotion on preosteoblast differentiation by up-regulating miR-23a through MAPK and JAK1/STAT3 pathways. Highlights: NGR1 induces MC3T3-E1 differentiation; miR-23a is positively regulated by NGR1; NGR1 regulates MAPK/JAK1/STAT3 through miR-23a.

摘要

越来越多的证据表明,三七总皂苷 R1(NGR1)对成骨细胞具有刺激作用。miR-23a 在成骨细胞分化中起着至关重要的作用。然而,NGR1 是否通过与miRs 相关的机制促进前成骨细胞分化仍未被探索。我们用 NGR1 预处理 MC3T3-E1,分析 Runx-2 和 Osx 的表达以及 ALP 活性。通过 Western blot 评估调节剂的磷酸化。使用 SB203580 和鲁索利替尼来降低调节剂的磷酸化。通过 qRT-PCR 验证 NGR1 对 miR-23a 的影响。我们分析了 NGR1 刺激和 miR-23a 抑制剂转染的 MC3T3-E1 中 Runx-2 和 Osx 的表达、ALP 活性以及调节剂的磷酸化。结果表明,NGR1 以浓度依赖的方式增强了 Runx-2 和 Osx 的表达以及 ALP 活性。NGR1 通过增加 MAPK、JAK1 和 STAT3 的磷酸化,对 Runx-2、Osx 和 ALP 活性表现出有效的促进作用。NGR1 导致 miR-23a 过表达,正向调节 Runx-2 和 Osx 的表达以及 ALP 活性。我们的结果表明,NGR1 预处理的 MC3T3-E1 中 miR-23a 抑制剂降低了 MAPK、JAK1 和 STAT3 的磷酸化。总之,NGR1 通过上调 miR-23a 通过 MAPK 和 JAK1/STAT3 途径对前成骨细胞分化表现出有效的促进作用。

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