title: MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2.
abstract: The elucidation of the molecular mechanisms that govern the differentiation of bone marrow stromal cells (BMSCs) could provide new insight into the treatment of bone loss diseases. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation, and differentiation. In the present study, we showed that miR-338-3p expression was significantly down-regulated during the osteoblastic differentiation of BMSCs. Additionally, miR-338-3p was up-regulated in ovariectomized (OVX) mice compared with sham mice. An in vitro analysis revealed that the over-expression of miR-338-3p can inhibit the expression of osteoblast differentiation markers such as Osterix (Osx), thus reducing osteoblast differentiation. Bioinformatic analysis and dual luciferase assays confirmed that miR-338-3p can repress gene expression by targeting Runx2 and Fgfr2. In the BMSCs derived from OVX mice, the inhibition of miR-338-3p partially rescued mineralization and osteoblast differentiation. Taken together, our data show that miR-338-3p plays an important role during osteoblast differentiation of BMSCs and serves as a potential modulator of osteoporosis via its effect on osteoblasts.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wan
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D011859:Radiography; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D035683:MicroRNAs; C000591274:Mirn338 microRNA, mouse; C493716:Runx2 protein, mouse; D008156:Luciferases; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2