Open AccessLong Noncoding RNA H 19 Promotes Osteoblast Differentiation Via TGF ‐β1/ S mad3/ HDAC Signaling Pathway by Deriving mi R ‐675
Author(s) -
Huang Yiping,
Zheng Yunfei,
Jia Lingfei,
Li Weiran
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2225
Subject(s) - gene knockdown , downregulation and upregulation , osteoblast , biology , microbiology and biotechnology , long non coding rna , mesenchymal stem cell , cellular differentiation , transforming growth factor , phosphorylation , cancer research , in vitro , cell culture , gene , biochemistry , genetics
A bstract 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‐β1 (TGF‐β1). The downregulation of TGF‐β1 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‐β1/Smad3/HDAC regulates osteogenic differentiation of hMSCs and may serve as a potential target for enhancing bone formation in vivo. S tem C ells 2015;33:3481–3492