Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675

• DOI: 10.1002/stem.2225
• Publication Date: 2015-09-29T16:14:54Z
• Authors: Yiping Huang; Yunfei Zheng; Lingfei Jia; Weiran Li
• Keywords: 0303 health sciences; Osteoblasts; Cell Differentiation; Mesenchymal Stem Cells; Histone Deacetylases; Transforming Growth Factor beta1; MicroRNAs; 03 medical and health sciences; Osteogenesis; Humans; RNA, Long Noncoding; Smad3 Protein; Signal Transduction

Abstract Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules at the transcriptional and post-transcriptional levels may play essential roles in differentiation of human bone marrow mesenchymal stem cell (hMSC). However, their functions remain unclear. Here, we showed that lncRNA H19 was significantly upregulated after induction osteoblast differentiation. Overexpression promoted osteogenic hMSCs vitro enhanced heterotopic formation vivo, whereas knockdown inhibited these effects. Subsequently, found miR-675, encoded by exon1 H19, partially responsible for pro-osteogenic effect H19. Investigating underlying mechanism, demonstrated H19/miR-675 mRNA protein expression transforming growth factor-β1 (TGF-β1). The downregulation TGF-β1 subsequently phosphorylation Smad3. Meanwhile, downregulated histone deacetylase (HDAC) 4/5, thus increased marker gene expression. Taken together, our results novel pathway H19/miR-675/TGF-β1/Smad3/HDAC regulates serve a potential target enhancing vivo. Stem Cells 2015;33:3481–3492