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    A RUNX2/MIR-3960/MIR-2861 regulatory feedback loop during mouse osteoblast differentiation

    J Biol Chem. 2011 Feb 15. [Epub ahead of print]

    These authors demonstrate that a newly described microRNA (miRNA) (miR-3960) has a regulatory role in osteoblast differentiation through a feedback loop with miR-2861and Runx2.
    Authors: Hu R, Liu W, Li H, et. al

    Our recent study showed that miR-2861 promotes osteoblast differentiation by targeting histone deacetylase 5 (HDAC5), resulting in increased runt related transcription factor 2 (Runx2) protein production. Here we identified another new microRNA (miRNA) (miR-3960) that played a regulatory role in osteoblast differentiation through a regulatory feedback loop with miR-2861. miR-3960 and miR-2861 were found clustered at the same loci. miR-3960 was transcribed during bone morphogenic protein 2 (BMP2) induced osteogenesis of ST2 stromal cells. Overexpression of miR-3960 promoted BMP2-induced osteoblastogenesis. However, the inhibition of miR-3960 expression attenuated the osteoblastogenesis. Homeobox A2 (Hoxa2), a repressor of Runx2 expression, was confirmed to be a target of miR-3960. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments confirmed that Runx2 bound to the promoter of the miR-3960/miR-2861 cluster. Furthermore, overexpression of Runx2 induced miR-3960/miR-2861 transcription, and block of Runx2 expression attenuated BMP2-induced miR-3960/miR-2861 transcription. Here, we reported that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast differentiation.

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