title: MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1.
abstract: OBJECTIVE
  Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs.
  
  
  METHODS
  First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214.
  
  
  RESULTS
  MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214.
  
  
  CONCLUSIONS
  MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Dawei
authors.initials: D
authors.lastname: Ge
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Cao
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Ge
authors.forename: Hongtao
authors.initials: H
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000503:physiopathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1