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Title: MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1

Osteoblast differentiation is a vital process in maintaining bone homeostasis in which various transcriptional factors, signaling molecules, and microRNAs (miRNAs) are involved. Recently, signal transducer and activator of transcription 1 (STAT1) has been found to play an important role in regulating osteoblast differentiation. Here, we identified that STAT1 expression was regulated by miR-194. Using mouse bone mesenchymal stem cells (BMSCs), we found that miR-194 expression was significantly increased following osteoblast differentiation induction. Overexpression of miR-194 by lentivirus-mediated gene transfer markedly increased osteoblast differentiation, whereas inhibition of miR-194 significantly suppressed osteoblast differentiation of BMSCs. Using a dual-luciferase reporter assay, a direct interaction between miR-194 and the 3′-untranslated region (UTR) of STAT1 was confirmed. Additionally, miR-194 regulated mRNA and protein expression of STAT1 in BMSCs. Further analysis showed that miR-194 overexpression promoted the nuclear translocation of runt-related transcription factor 2 (Runx2), which is critical for osteoblast differentiation. In contrast, inhibition of miR-194 blocked the nuclear translocation of Runx2. Moreover, overexpression of STAT1 significantly blocked Runx2 nuclear translocation and osteoblast differentiation mediated by miR-194 overexpression. Taken together, our data suggest that miR-194 regulates osteoblast differentiation through modulating STAT1-mediated Runx2 nuclear translocation. - Highlights: • Overexpression of miR-194 significantly increased osteoblast differentiation. • miR-194more » directly targeted the 3′- UTR of STAT1. • miR-194 regulated the expression of STAT1. • Overexpression of miR-194 promoted the nuclear translocation of Runx2.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3]
  1. Department of Emergency, Shannxi Province People's Hospital, Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710052 (China)
  2. Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004 (China)
  3. Department of Immunology and Pathogenic Biology, Medical School, Xi'an Jiaotong University, Xi'an 710061 (China)
Publication Date:
OSTI Identifier:
22462029
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 460; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CONNECTIVE TISSUE CELLS; GENES; HOMEOSTASIS; INHIBITION; LUCIFERASE; MESSENGER-RNA; MICE; MOLECULES; SIGNALS; STEM CELLS; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSDUCERS; TRANSLOCATION