The function and mechanism of the miR-210-3p/KRAS axis in bone marrow-derived mesenchymal stem cell from patients with osteoporosis
The function and mechanism of the miR-210-3p/KRAS axis in bone marrow-derived mesenchymal stem cell from patients with osteoporosis
复制标题
骨质疏松患者骨髓间充质干细胞中miR-210-3p/KRAS轴的功能及机制
DOI：
10.1002/term.3215
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发表时间：
2021-07-06
影响因子：
3.3
通讯作者：
Chen, Shijie
中科院分区：
文献类型：
--
作者：
Hu, Minghua;Zhu, Xi;Chen, Shijie
骨髓间充质干细胞（BMSC）成脂和成骨过程中的稳态失调可导致病理后果，在骨质疏松症的发病机制中起着关键作用。在本研究中，我们证明了miR-210- 3 p在骨质疏松症患者的股骨中异常上调，在成骨分化的BMSCs中异常下调。预测的候选miRNAs的靶点在多能干细胞分化信号传导中富集。KRAS作为KRAS/MAPK/ERK信号通路中的重要因子，在成骨分化的BMSCs中表达上调。在骨髓间充质干细胞中，KRAS的表达水平显示降低，而miR-210- 3 p的表达水平显示增加。在正常BMSCs中，miR-210- 3 p过表达或KRAS沉默显著抑制成骨分化和MAPK信号转导的激活。miR-210- 3 p直接靶向KRAS并抑制KRAS表达。miR-210- 3 p过表达对KRAS表达、MAPK信号传导和BMSC成骨分化的影响被KRAS过表达显著逆转。总之，miR-210- 3 p通过靶向KRAS和抑制MAPK信号通路抑制正常BMSC成骨分化; KRAS过表达可逆转miR-210- 3 p过表达的抑制作用。
The disturbance of homeostasis in bone marrow-derived mesenchymal stem cell (BMSC) adipogenesis and osteogenesis could result in pathologic consequences that plays a critical role in osteoporosis pathogenesis. In the present study, we demonstrated that miR-210-3p was abnormally upregulated within the femur of osteoporosis patients and abnormally downregulated in osteogenically differentiated BMSCs. The predicted targets of candidate miRNAs were enriched in the Pluripotent stem cell differentiation signaling. KRAS, as a vital factor of the KRAS/MAPK/ERK signaling, was upregulated in osteogenically differentiated BMSCs. In osteoporosis-BMSCs, the expression level of KRAS showed to be decreased, whereas the expression level of miR-210-3p showed to be increased. Within normal-BMSCs, miR-210-3p overexpression or KRAS silencing significantly inhibited the osteogenic differentiation and the activation of the MAPK signaling. miR-210-3p directly targeted KRAS and inhibited KRAS expression. The effects of miR-210-3p overexpression upon KRAS expression, MAPK signaling, and BMSC osteogenic differentiation were significantly reversed by KRAS overexpression. Altogether, miR-210-3p suppresses normal BMSC osteogenic differentiation through targeting KRAS and suppressing the MAPK signaling; KRAS overexpression could reverse the suppressive effects of miR-210-3p overexpression.