1 Section VI. Building 18.4, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Secretariat, The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet3 Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology, Odense University Hospital, J.B. Winsløws Vej 25, 1, DK-5000 Odense C, Denmark. Electronic address: firstname.lastname@example.org Section VI. Building 18.4, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC. We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary, miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low bone mass diseases, e.g. osteoporosis.
Biochimica Et Biophysica Acta. Molecular Cell Research, 2014, Vol 1843, Issue 9, p. 2114-21