title: MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1.
abstract: 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.
authors: Department of Emergency, Shannxi Province People's Hospital, Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710052, China.
authors: Jun
authors: J
authors: Li
authors: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
authors: Xijing
authors: X
authors: He
authors: Department of Emergency, Shannxi Province People's Hospital, Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710052, China.
authors: Wenzhi
authors: W
authors: Wei
authors: Department of Immunology and Pathogenic Biology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: xiaobozhouxa@163.com.
authors: Xiaobo
authors: X
authors: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000502:physiology*
chemical_list: C554845:MIRN194 microRNA, mouse; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse
keywords: Osteoblast differentiation; Runx2; STAT1; miR-194