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Here, we show that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs. miRNA array profiling and further validation by quantitative RT-PCR (qRT-PCR) revealed that miR-138 was down-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore, overexpression of miR-138 reduced ectopic bone formation in vivo by 85%, and conversely, in vivo bone formation was enhanced by 60% when miR-138 was antagonized. Target prediction analysis and experimental validation by luciferase 3\u2032 UTR reporter assay confirmed focal adhesion kinase, a kinase playing a central role in promoting osteoblast differentiation, as a bona fide target of miR-138. We show that miR-138 attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway. Our findings suggest that pharmacological inhibition of miR-138 by antimiR-138 could represent a therapeutic strategy for enhancing bone formation in vivo.<\/jats:p>","DOI":"10.1073\/pnas.1016758108","type":"journal-article","created":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T22:34:26Z","timestamp":1301351666000},"page":"6139-6144","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":417,"title":["MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo"],"prefix":"10.1073","volume":"108","author":[{"given":"Tilde","family":"Eskildsen","sequence":"first","affiliation":[{"name":"Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of South Denmark, DK-5000 Odense C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Taipaleenm\u00e4ki","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of South Denmark, DK-5000 Odense C, Denmark;"},{"name":"Department of Medical Biochemistry and Genetics, University of Turku, 20520, Turku, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stenvang","sequence":"additional","affiliation":[{"name":"Wilhelm Johansen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark;"},{"name":"Department of microRNA Research, Santaris Pharma, DK-2970 H\u00f8rsholm, Denmark;"},{"name":"Institute of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basem M.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of South Denmark, DK-5000 Odense C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Ditzel","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of South Denmark, DK-5000 Odense C, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Yael","family":"Nossent","sequence":"additional","affiliation":[{"name":"Wilhelm Johansen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Bak","sequence":"additional","affiliation":[{"name":"Wilhelm Johansen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakari","family":"Kauppinen","sequence":"additional","affiliation":[{"name":"Wilhelm Johansen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark;"},{"name":"Department of microRNA Research, Santaris Pharma, DK-2970 H\u00f8rsholm, Denmark;"},{"name":"Copenhagen Institute of Technology, Aalborg University, DK-2750 Ballerup, Denmark; 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