A non-coding transcript of nephronectin promotes osteoblast differentiation by modulating microRNA functions.

We investigated the roles of the non-coding transcripts and found that expression of a fragment containing the 3'-untranslated region (3'-UTR) of nephronectin in osteoblast progenitor cells MC3T3-E1 promoted cell differentiation dramatically. We hypothesized that the ectopically expressed 3'-UTR binds microRNAs and modulates their functions. β-Catenin and GSK3β were up-regulated in the 3'-UTR-transfected cells, contributing to the increased cell differentiation, through reduction of EGFR and ERK phosphorylation. Activator of GSK3β promoted differentiation, while inhibitor of GSK3β blocked differentiation. Our results indicate that the non-coding transcripts are important in regulating cell activities and may have potential application for modulating endogenous microRNA functions.