title: MiR-133 is Involved in Estrogen Deficiency-Induced Osteoporosis through Modulating Osteogenic Differentiation of Mesenchymal Stem Cells.
abstract: BACKGROUND
  MiR-133 expression is dysregulated in postmenopausal osteoporosis. However, its role in postmenopausal osteoporosis is still not well understood. In the current study, we explore how estrogen deficiency affects miR-133 expression and how miR-133 is involved in osteogenic differentiation of mesenchymal stem cells (MSCs).
  
  
  METHODS
  qRT-PCR analysis was performed to assess miR-133 expression in MSCs isolated from bone marrow of an ovariectomized (OVX) animal model and postmenopausal osteoporosis patients (PMOP) and their corresponding controls. The binding between miR-133 and predicted target SLC39A1 was verified using dual luciferase assay and Western blot analysis. The effect of miR-133 and SLC39A1 on osteogenic differentiation of MSCs was assessed through measuring alkaline phosphatase (ALP), mineralization nodules, and osteoblast-specific genes Runx2 and Osterix expression.
  
  
  RESULTS
  miR-133 expression is significantly enhanced as a result of estrogen deficiency. Its overexpression is negatively correlated to osteogenic differentiation of hMSCs. SLC39A1 showed an inverse expression trend to miR-133 during the differentiation. miR-133 can directly target 3'UTR of SLC39A1 and thereby modulate its expression in hMSCs. The miR-133-SLC39A1 axis might play an important role in osteogenic differentiation of hMSCs. SLC39A1 can promote ALP activity and formation of mineralization nodules. In addition, SLC39A1 expression level is also positively correlated with RUNX2 and Osterix.
  
  
  CONCLUSIONS
  Estrogen deficiency is associated with miR-133 overexpression. MiR-133 can induce postmenopausal osteoporosis by weakening osteogenic differentiation of hMSCs, at least partly through repressing SLC39A1 expression.
authors.affiliation: Department of Orthopaedic Traumatology, Central Hospital of Jinan, Affiliated to Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Hao
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Orthopedics, Yantai Yuhuangding Hospital, Affiliated to Qingdao University Medical College, Yantai, Shandong, China (mainland).
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedics Surgery, The First Hospital of Hebei Medial University, Shijiazhuang, Hebei, China (mainland).
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004967:Estrogens / Q000172:deficiency*; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000209:etiology* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D050659:Core Binding Factor Alpha 1 Subunit; D004967:Estrogens; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C010078:alizarin; D008156:Luciferases; D000469:Alkaline Phosphatase