MicroRNA-98-5p prevents bone regeneration by targeting high mobility group AT-Hook 2

MicroRNA-98-5p 通过靶向高迁移率组 AT-Hook 2 来阻止骨再生

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作者:Feng Zheng, Furong Wang, Zhe Xu

Abstract

MicroRNAs (mRNAs or miRs) serve an important role in the regulation of gene expression. In the present study, the role of miR-98-5p in bone regeneration was determined. Three osteoblast cell models were established, including primary human stem cells (BMMSC), mouse BMMSC's and MC3T3-E1 cells. miR-98-5p expression was determined using reverse transcription-quantitative (RT-q)PCR. Osteoblast markers, including alkaline phosphatase, runt related transcription factor 2 and transcription factor Sp7, were determined using RT-qPCR and western blot analysis, respectively. Alkaline phosphatase activity was determined in the present study and cell proliferation and apoptosis assays were performed. Furthermore, an association between miR-98-5p and high mobility group AT-Hook 2 (HMGA2) was revealed. This association was determined using TargetScan and a dual luciferase reporter assay. The current study demonstrated that miR-98-5p was downregulated during osteogenic differentiation and further demonstrated that HMGA2 may be a direct target of miR-98-5p. The results also demonstrated that miR-98-5p upregulation significantly inhibited the osteogenic differentiation of MC3T3-E1 cells, an effect that was reversed by an increased HMGA2 expression. Additionally, the results revealed that miR-98-5p upregulation inhibited MC3T3-E1 cell viability and induced cell apoptosis and these effects were eliminated by HMGA2 overexpression. In conclusion, miR-98-5p may prevent bone regeneration through inhibiting osteogenic differentiation and osteoblast growth by targeting HMGA2.

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