1. Investigation of the role of the miR17-92 cluster in BMP9-induced osteoblast lineage commitment.
- Author
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Zhang Y, Jing X, Li Z, Tian Q, Wang Q, and Chen X
- Subjects
- Cell Differentiation, Growth Differentiation Factor 2 genetics, MicroRNAs genetics, Osteoblasts, Osteogenesis genetics, Mesenchymal Stem Cells
- Abstract
Background: Bone morphogenetic protein 9 (BMP9) has been identified as a crucial inducer of osteoblastic differentiation in mesenchymal stem cells (MSCs). Although microRNAs (miRNAs) are known to play a role in MSC osteogenesis, the mechanisms of action of miRNAs in BMP9-induced osteoblastic differentiation remain poorly understood., Methods: In this study, we investigate the possible role of the miR17-92 cluster in the BMP9-induced osteogenic differentiation of MSCs by using both in vitro and in vivo bone formation assays., Results: The results show that miR-17, a member of the miR17-92 cluster, significantly impairs BMP9-induced osteogenic differentiation. This impairment is effectively rescued by a miR-17 sponge, an antagomiR sequence against miR-17. Using TargetScan and the 3'-untranslated region luciferase reporter assays, we show that the direct target of miR-17 is the retinoblastoma gene (RB1), a gene that is pivotal to osteoblastic differentiation. We also confirm that RB1 is essential for the miR-17 effects on osteogenesis., Conclusion: Our results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9., (© 2021. The Author(s).)
- Published
- 2021
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