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Bone Abstracts (2014) 3 PP123 | DOI: 10.1530/boneabs.3.PP123

Cell biology: osteoblasts and bone formation

miR-468 controls Runx2 expression during early differentiation of Runx2 in mice

Owen Cabon1,2 & Valerie Geoffroy1,2


1UMR1132, Paris, France; 2Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

We investigated the ability of microRNAs to regulate osteoblast differentiation by controlling distinct aspects of the differentiation process. We have identified by microRNAs microarray a set of miRNAs that are differentially regulated during differentiation of the two osteoblast cell lines MC3T3-E1 and C3H10T1/2. We focused on miR-468 that is a potential regulator of Runx2.

In our microarray analysis miR-468 was expressed at a high level and was strongly down regulated during osteoblast differentiation. The down regulation of the expression of miR-468 well matches with the regulation of the expression of Runx2 that is increased during the early stage of osteoblast differentiation. After induction of osteoblast differentiation, miR-468 expression is decreasing from day 3 over time and was highly consistent with the microarray data.

One single target site for miR-468 was present in the first 500 bp of the 3′UTR of the Runx2 gene. These first 500 bp are able to mediate a 40 and 60% inhibition of the Runx2 activity in MC3T3-E1 and C3H10T1/2 cells respectively. We demonstrate that Runx2 expression was specifically down-regulated by miR-468. We showed by western blot and using reporter plasmids that miR-468 reduced Runx2 expression, inhibited its transcriptional activity and decreased expression of osteoblastic markers (SP7, BSP, type1 collagen) that are regulated by Runx2. The inhibitory effect of miR-468 on Runx2 expression was abolished when its target site on the 3′UTR of Runx2 is mutated.

All together these results indicate that Runx2 is a direct target of miR-468. Our findings suggest that miR-468 acts as Runx2 attenuators to antagonize osteoblast differentiation in pre-osteoblastic cells and possibly in BMSCs. This further indicates that a down-regulation of miR-468 may be required to release the factor Runx2 from repression and to induce osteoblast differentiation.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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