MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1

Journal Article · Fri May 01 04:00:00 EDT 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.03.059· OSTI ID:22462029

Li, Jun ^[1]; He, Xijing ^[2]; Wei, Wenzhi ^[1]; Zhou, Xiaobo ^[3]

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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)

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-194 directly targeted the 3′- UTR of STAT1. • miR-194 regulated the expression of STAT1. • Overexpression of miR-194 promoted the nuclear translocation of Runx2.

• OSTI ID: 22462029
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 460; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CONNECTIVE TISSUE CELLS
GENES
HOMEOSTASIS
INHIBITION
LUCIFERASE
MESSENGER-RNA
MICE
MOLECULES
SIGNALS
STEM CELLS
TRANSCRIPTION
TRANSCRIPTION FACTORS
TRANSDUCERS
TRANSLOCATION