柚皮苷通过miR-26a/Ski轴的介导作用促进骨髓间充质干细胞的成骨潜能。
Naringin promotes osteogenic potential in bone marrow-derived mesenchymal stem cells via mediation of miR-26a/Ski axis.
作者信息
Zou Jiawei, Zhou Longze, Liu Guoqiang, Zhang Ying, Zeng Lingguo
机构信息
Department of Traumatic Orthopedics, Yuebei People's Hospital Affiliated to Shantou University School of Medicine, Shaoguan 512026, China.
出版信息
Bone Rep. 2024 Nov 13;23:101815. doi: 10.1016/j.bonr.2024.101815. eCollection 2024 Dec.
BACKGROUND
Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease, which seriously affects the quality of life of patients. Naringin has protective effect on ONFH. In present study, we aimed to investigate the mechanism of Naringin regulating miR-26a in ONFH.
METHODS
Two sequencing datasets (GSE89587 for micro-RNA, GSE123568 for mRNA) related to ONFH were obtained from the GEO database for bioinformatics analysis. Bone marrow-derived mesenchymal stem cells (BMSCs) were treated with adipogenic medium (AM) or osteogenic medium (OM), and then treated with 10 μM, 100 μM or 1000 μM Naringin. Gene and protein levels were detected by RT-qPCR and Western blotting. ALP activity and alizarin red staining (ARS) were applied to investigate the osteogenic differentiation of BMSCs. Oil red O staining was performed to test adipogenic differentiation. The content of triglycerides (TG) in BMSCs was detected by TG detection kit. Double luciferase reporter gene measured the interaction between miR-26a and Ski.
RESULTS
Bioinfomatic analyses indicated a significant downregulation of miR-26a and a significant upregulation of Ski in the peripheral blood of patients with ONFH. Naringin significantly promoted the osteogenic differentiation, and increased the ALP activity and ARS. Meanwhile, it decreased the adipogenic differentiation and inhibited TG levels. In addition, miR-26a was downregulated and Ski was increased in AM-treated BMSCs, while miR-26a was upregulated and Ski was decreased in OM-treated BMSCs. Furthermore, miR-26a promoted the osteogenic differentiation and suppressed the adipogenic differentiation in BMSCs. Moreover, Naringin enhanced osteogenic potential in BMSCs was reversed by knockdown of miR-26a or overexpression of Ski.
CONCLUSION
Naringin could promote osteogenic differentiation of BMSCs via mediation of miR-26a/Ski axis. Thereby, Naringin might be a new agent for ONFH treatment.
背景
股骨头坏死（ONFH）是一种常见的骨科疾病，严重影响患者的生活质量。柚皮苷对ONFH具有保护作用。在本研究中，我们旨在探讨柚皮苷在ONFH中调节miR-26a的机制。
方法
从GEO数据库中获取两个与ONFH相关的测序数据集（用于 micro-RNA 的 GSE89587 和用于 mRNA 的 GSE123568）进行生物信息学分析。用成脂培养基（AM）或成骨培养基（OM）处理骨髓间充质干细胞（BMSCs），然后分别用10 μM、100 μM或1000 μM柚皮苷处理。通过RT-qPCR和蛋白质印迹法检测基因和蛋白水平。应用碱性磷酸酶（ALP）活性和茜素红染色（ARS）研究BMSCs的成骨分化。进行油红O染色检测成脂分化。用甘油三酯（TG）检测试剂盒检测BMSCs中TG的含量。双荧光素酶报告基因检测miR-26a与Ski之间的相互作用。
结果
生物信息学分析表明，ONFH患者外周血中miR-26a显著下调，Ski显著上调。柚皮苷显著促进成骨分化，增加ALP活性和ARS。同时，它降低了成脂分化并抑制了TG水平。此外，在AM处理的BMSCs中miR-26a下调而Ski上调，而在OM处理的BMSCs中miR-26a上调而Ski下调。此外，miR-26a促进BMSCs的成骨分化并抑制其成脂分化。而且，敲低miR-26a或过表达Ski可逆转柚皮苷增强的BMSCs成骨潜能。
结论
柚皮苷可通过miR-26a/Ski轴介导促进BMSCs的成骨分化。因此，柚皮苷可能是一种治疗ONFH的新型药物。
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