In the present study, we identified miR-346 as a positive regulator of the 
osteogenic differentiation of hBMSCs. We found that miR-346 was highly expressed during the course of osteogenic differentiation. Overexpression of miR-346 in hBMSCs enhanced osteogenic differentiation, whereas inhibition of miR-346 suppressed their osteogenic potential. miRNAs, as novel regulators of target gene expression, play important roles in regulation of stem cell differentiation into osteoblasts by controlling the levels of critical factors. For instance, miR-138, which is down-regulated during AbMole Capromorelin tartrate osteoblast differentiation of hBMSCs, functions as a negative regulator of osteogenic differentiation by targeting FAK and suppressing the FAK-ERK1/2 signaling pathway. miR-204 inhibits osteoblast differentiation of BMSCs, while adipocyte differentiation is promoted when miR-204 is overexpressed in these cells. miR20a AbMole Diniconazole promotes the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPARc, Bambi and Crim1, the negative regulators of BMP signaling. Here, we report that GSK-3b is a direct target of miR-346 in hBMSCs. Our data indicate that miR-346 overexpression significantly down-regulates GSK-3b by directly targeting the 39UTR of GSK-3b mRNA confirmed using luciferase-reporter-gene assays, and this effect was largely eliminated when the sites in GSK-3b 39UTR targeted by miR-346 were mutated. Moreover, miR-346 overexpression in hBMSCs resulted in upregulation of GSK-3b protein level without changing its mRNA expression, confirming that miR-346 regulates GSK-3b expression at a post-transcription level. GSK-3b, an isoform of GSK-3, is implicated in various biological processes including cell growth, differentiation and apoptosis. Mounting evidence indicates that GSK-3b inhibition promotes bone formation in vivo. In recent years, GSK-3b has been reported to play important roles in regulating osteoblast differentiation. Gambardella et al. have shown that inhibition of GSK-3b promotes osteogenic differentiation of mesenchymal progenitors but not adipogenic differentiation. Jang et al. found that GSK-3b inactivation upon receptor activator of NF-kB ligand stimulation is crucial for osteoclast differentiation. In this study, we demonstrate that GSK-3b is a functional target of miR-346. Our data show that osteogenic differentiation of hBMSCs is suppressed by overexpression of GSK-3b inmiR-346-overexpressing cells, while GSK3b siRNA almost completely blockes the inhibitory role of antimiR-346 on osteogenic differentiation, suggesting that miR-346regulated osteogenic differentiation is GSK-3b-dependent. Our data further demonstrate that miR-346-mediated downregulation of GSK-3b leads to activation of Wnt/b-catenin signaling in hBMSCs. Firstly, miR-346 overexpression significantly increased total and activated b-catenin expression. Secondly, immunofluorescence staining showed increased b-catenin nuclear accumulation in miR-346�Coverexpressing cells compared to miRcontrol cells. Thirdly, miR-346 overexpression increased TCF/ LEF transcriptional activity, and this effect was blocked by antimiR-346. In addition, b-catenin knockdown in miR-346-overexpressing cells almost completely blocked the positive effect of miR346 on osteogenic differentiation. Consistent with these findings, miR-346 overexpression was found to enhance the expression of several b-catenin downstream genes in hBMSCs. In conclusion, this study identified miR-346 as a positive regulator of human osteogenesis, acting by targeting GSK-3b and activating Wnt/b-catenin signaling in hBMSCs. Our findings suggest that miR-346 may be a useful target in the treatment of pathological conditions of bone loss.