title: MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion.
abstract: This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 β (GSK3β), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3β, ATP8A2, and EIF4EBP1, respectively.
authors.affiliation: Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. sunmishu@126.com.
authors.forename: Tianhao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. klleunga@hku.hk.|Shenzhen Key Laboratory for Innovative Technology, The University of Hong Kong Shenzhen Hospital, Shenzhen 518000, China. klleunga@hku.hk.
authors.forename: Frankie
authors.initials: F
authors.lastname: Leung
authors.affiliation: Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. wwlu@hku.hk.|Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518000, China. wwlu@hku.hk.
authors.forename: William W
authors.initials: WW
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002452:Cell Count; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D039642:Eukaryotic Initiation Factors; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics; D049294:Phospholipid Transfer Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D013324:Strontium / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C583174:MIRN138 microRNA, mouse; C574758:MIRN675 microRNA, mouse; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D049294:Phospholipid Transfer Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C545446:ATP8a2 protein, mouse; D000251:Adenosine Triphosphatases; D013324:Strontium
keywords: LRP5; adhesion and apoptosis; bone; cell proliferation; differentiation; microRNA or miRNA; strontium; target