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学科主题口腔医学
Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-beta 1/Smad3/HDAC Signaling Pathway by Deriving miR-675
Huang, Yiping1; Zheng, Yunfei2; Jia, Lingfei2,3; Li, Weiran1
关键词Mesenchymal Stem Cells Osteoblast Differentiation Lncrna Mirna H19 Mir-675
刊名STEM CELLS
2015-12-01
DOI10.1002/stem.2225
33期:12页:3481-3492
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
研究领域[WOS]Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
关键词[WOS]MESENCHYMAL STEM-CELLS ; GROWTH-FACTOR-BETA ; BONE-FORMATION ; OSTEOGENIC DIFFERENTIATION ; TGF-BETA ; ECTOPIC OSTEOGENESIS ; CANCER METASTASIS ; EMBRYONIC STEM ; MESSENGER-RNA ; STROMAL CELLS
英文摘要

Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules at the transcriptional and post-transcriptional levels and may play essential roles in the differentiation of human bone marrow mesenchymal stem cell (hMSC). However, their roles and functions remain unclear. Here, we showed that lncRNA H19 was significantly upregulated after the induction of osteoblast differentiation. Overexpression of H19 promoted osteogenic differentiation of hMSCs in vitro and enhanced heterotopic bone formation in vivo, whereas knockdown of H19 inhibited these effects. Subsequently, we found that miR-675, encoded by exon1 of H19, promoted osteoblast differentiation of hMSCs and was partially responsible for the pro-osteogenic effect of H19. Investigating the underlying mechanism, we demonstrated that H19/miR-675 inhibited mRNA and protein expression of transforming growth factor-beta 1 (TGF-beta 1). The downregulation of TGF-beta 1 subsequently inhibited phosphorylation of Smad3. Meanwhile, H19/miR-675 downregulated the mRNA and protein levels of histone deacetylase (HDAC) 4/5, and thus increased osteoblast marker gene expression. Taken together, our results demonstrated that the novel pathway H19/miR-675/TGF-beta 1/Smad3/HDAC regulates osteogenic differentiation of hMSCs and may serve as a potential target for enhancing bone formation in vivo.

语种英语
WOS记录号WOS:000365049000014
项目编号81402235 ; PKUSS20140104
资助机构National Natural Science Foundation of China ; Foundation of Peking University School and Hospital of Stomatology
引用统计
被引频次:49[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50195
专题北京大学口腔医学院_牙周科
北京大学口腔医学院_口腔正畸科
北京大学口腔医学院_中心实验室
作者单位1.Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China
2.Peking Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, Beijing 100081, Peoples R China
3.Peking Univ, Cent Lab, Sch & Hosp Stomatol, Beijing 100081, Peoples R China
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GB/T 7714
Huang, Yiping,Zheng, Yunfei,Jia, Lingfei,et al. Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-beta 1/Smad3/HDAC Signaling Pathway by Deriving miR-675[J]. STEM CELLS,2015,33(12):3481-3492.
APA Huang, Yiping,Zheng, Yunfei,Jia, Lingfei,&Li, Weiran.(2015).Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-beta 1/Smad3/HDAC Signaling Pathway by Deriving miR-675.STEM CELLS,33(12),3481-3492.
MLA Huang, Yiping,et al."Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-beta 1/Smad3/HDAC Signaling Pathway by Deriving miR-675".STEM CELLS 33.12(2015):3481-3492.
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