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. 2014 Jun 3;9(6):e98063. doi: 10.1371/journal.pone.0098063

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© 2014 Cheung et al

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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miR-146a down-regulated SMAD2 and SMAD3 protein levels, resulting in an attenuation of TGF-β signaling following TGF-β3 stimulation. Stimulation by TGF-β3 down-regulated the expression of miR-146a indicating a double negative feedback loop and thus a potential auto-regulatory mechanism. Overexpression of miR-146a under basal condition revealed a modest, but positive effect on osteogenesis related gene expression and is likely part of a miR network involved in promoting osteogenesis. The inhibitory effect of miR-146a on SMAD4 was previously reported by Zhong et al [31] and was not reevaluated in this study.