Upregulation of long non-coding RNA HIF 1α-anti-sense 1 induced by transforming growth factor-β-mediated targeting of sirtuin 1 promotes osteoblastic differentiation of human bone marrow stromal cells

The present study aimed to investigate the regulatory mechanism of long non-coding RNA hypoxia-inducible factor 1 alpha-anti-sense 1 (IncRNA HIF1 alpha-AS1) in osteoblast differentiation as well as its targeting by sirtuin 1 (SIRT1), which may be inhibited by transforming growth factor (TGF)-beta in bone marrow stromal cells (BMSCs). Real-time polymerase chain reaction (PCR), western blot analysis, IncRNA PCR arrays and chromatin immunoprecipitation were performed in order to examine the interference of SIRT1 expression by TGF-beta, the effects of SIRT1 overexpression on lncRNA HIF1 alpha-AS1 and the regulation of the expression of homeobox (HOX)D10, which promotes BMSC differentiation, by IncRNA HIF1 alpha-AS1. The results showed that TGF-beta interfered with SIRT1 expression. Furthermore, IncRNA HIF1 alpha-AS1 was significantly downregulated following overexpression of SIRT1. In addition, low expression of HIF1 alpha-AS1 was sufficient to block the expression of HOXD10. The present study further demonstrated that downregulation of HOXD10 by HIF1 alpha-AS1 interfered with acetylation, and subsequently resulted in the inhibition of osteoblast differentiation. These results suggested that HIF1 alpha-AS1 is an essential mediator of osteoblast differentiation, and may thus represent a gene-therapeutic agent for the treatment of human bone diseases.