Abstract
BackgroundBone 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.MethodsIn 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.ResultsThe 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.ConclusionOur results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9.
Highlights
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to self-renew and the ability to differentiate into osteoblastic, adipogenic, myogenic, and chondrogenic lineages [1,2,3,4,5]
MiR‐17 is significantly downregulated during Bone morphogenetic protein 9 (BMP9)‐induced osteogenic differentiation To determine the role of the miR-17-92 cluster in the osteogenic differentiation of mesenchymal stem cells (MSCs), we used touchdown quantitative real‐time PCR (TqPCR) to analyze the expression of miR-17-92 cluster members in Immortalized mouse embryonic fibroblasts (iMEFs)
Our results showed that miR17 expression dramatically decreased from day 3 to day 7 in BMP9-induced iMEFs compared to the miR control group
Summary
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to self-renew and the ability to differentiate into osteoblastic, adipogenic, myogenic, and chondrogenic lineages [1,2,3,4,5]. Osteogenic differentiation of MSCs is a complex process that is tightly regulated by key molecules and several signaling pathways [8, 9] One such key regulator is a group of growth factors known as bone morphogenetic proteins (BMPs). Bone morphogenetic protein 9 (BMP9) has been identified as a crucial inducer of osteoblastic differentiation in mesenchymal stem cells (MSCs). 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
