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微小RNA-139-5p通过靶向Wnt/β-连环蛋白信号通路抑制骨髓间充质干细胞成骨分化

miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/β-Catenin Signaling Pathway.

作者信息

Long Haitao, Sun Buhua, Cheng Liang, Zhao Shushan, Zhu Yong, Zhao Ruibo, Zhu Jianxi

机构信息

Department of Orthopedics, Xiangya Hospital of Central South University , Changsha, Hunan, People's Republic of China .

出版信息

DNA Cell Biol. 2017 Aug;36(8):715-724. doi: 10.1089/dna.2017.3657. Epub 2017 Jun 16.

Abstract

Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated. Calcium-rich deposit (mineralization) is also a typical osteogenic differentiation marker that could be visualized by alizarin red S (ARS) staining. Inhibiting miR-139-5p notably promotes the hBMSC osteoblast differentiation, which, however, will be reduced by overexpressed miR-139-5p. This result has been made based on the alternations of ALP activity, ARS staining, as well as expression of osteogenic genes, including runt-related gene-2 (Runx2), collagen I (Col-1), and osteocalcin (OCN). miR-139-5p exerts its role in BMSC osteogenesis most probably through the Wnt/β-catenin pathway, by direct targeting CTNNB1 and frizzled 4 (FZD4), essential factors of Wnt/β-catenin pathway. In conclusion, according to the present study, inhibiting miR-139-5p could be a promising strategy in hBMSC osteogenesis.

摘要

间充质干细胞(MSCs)的成骨作用在骨修复中发挥了必要作用。根据一些报道,微小RNA参与细胞的不同生理活动,包括细胞分化。本研究调查了miR-139-5p在人骨髓间充质干细胞(hBMSCs)成骨分化中所起的作用。除了miR-139-5p,还研究了碱性磷酸酶(ALP)的作用,ALP是一种膜结合金属酶,被认为是早期成骨分化标志物。富含钙的沉积物(矿化)也是一种典型的成骨分化标志物,可通过茜素红S(ARS)染色观察到。抑制miR-139-5p显著促进hBMSC向成骨细胞分化,然而,过表达miR-139-5p会使其作用减弱。这一结果是基于ALP活性、ARS染色以及成骨基因表达的变化得出的,这些成骨基因包括与 runt 相关的基因-2(Runx2)、I 型胶原蛋白(Col-1)和骨钙素(OCN)。miR-139-5p最有可能通过Wnt/β-连环蛋白途径在BMSC成骨过程中发挥作用,它直接靶向Wnt/β-连环蛋白途径的关键因子CTNNB1和卷曲蛋白4(FZD4)。总之,根据本研究,抑制miR-139-5p可能是促进hBMSC成骨的一种有前景的策略。

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