miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/β-Catenin Signaling Pathway
miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/β-Catenin Signaling Pathway
复制标题
miR-139-5p 通过靶向 Wnt/β-Catenin 信号通路抑制 BMSC 成骨
DOI：
10.1089/dna.2017.3657
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发表时间：
2017-08-01
影响因子：
3.1
通讯作者：
Zhu, Jianxi
中科院分区：
文献类型：
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作者：
Long, Haitao;Sun, Buhua;Zhu, Jianxi
间充质干细胞（MSC）的成骨作用在骨修复中发挥着必要的作用。根据一些报道，microRNA参与细胞的不同生理活动，包括细胞分化。本研究探讨miR-139- 5 p在人骨髓间充质干细胞（hBMSCs）成骨分化中的作用。除了miR-139- 5 p之外，还研究了碱性磷酸酶（ALP）的作用，ALP是一种被认为是早期成骨分化标志物的膜结合金属酶。富钙存款（矿化）也是一个典型的成骨分化标志物，可以通过茜素红S（ARS）染色可视化。抑制miR-139- 5 p显著促进hBMSC成骨细胞分化，然而，过表达的miR-139- 5 p将降低hBMSC成骨细胞分化。这一结果是基于ALP活性、ARS染色以及成骨基因表达的变化，包括Runx 2、胶原I和骨钙素。miR-139- 5 p通过直接靶向Wnt/beta-catenin通路的关键因子CTNNB 1和Frizzled 4（FZD 4），在BMSC成骨中发挥作用。总之，根据本研究，抑制miR-139- 5 p可能是hBMSC成骨中有前途的策略。
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/beta-catenin pathway, by direct targeting CTNNB1 and frizzled 4 (FZD4), essential factors of Wnt/beta-catenin pathway. In conclusion, according to the present study, inhibiting miR-139-5p could be a promising strategy in hBMSC osteogenesis.