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

Xu,Yao; Wang,Shilong; Tang,Chaoliang; Chen,Wenjun

doi:10.3892/mmr.2015.4415

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

Authors:
- Yao Xu
- Shilong Wang
- Chaoliang Tang
- Wenjun Chen
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Affiliations: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China
Published online on: October 1, 2015 https://doi.org/10.3892/mmr.2015.4415
Pages: 7233-7238
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the regulatory mechanism of long non-coding RNA hypoxia-inducible factor 1α-anti‑sense 1 (lncRNA HIF1α-AS1) in osteoblast differentiation as well as its targeting by sirtuin 1 (SIRT1), which may be inhibited by transforming growth factor (TGF)‑β in bone marrow stromal cells (BMSCs). Real‑time polymerase chain reaction (PCR), western blot analysis, lncRNA PCR arrays and chromatin immunoprecipitation were performed in order to examine the interference of SIRT1 expression by TGF‑β, the effects of SIRT1 overexpression on lncRNA HIF1α‑AS1 and the regulation of the expression of homeobox (HOX)D10, which promotes BMSC differentiation, by lncRNA HIF1α‑AS1. The results showed that TGF‑β interfered with SIRT1 expression. Furthermore, lncRNA HIF1α‑AS1 was significantly downregulated following overexpression of SIRT1. In addition, low expression of HIF1α‑AS1 was sufficient to block the expression of HOXD10. The present study further demonstrated that downregulation of HOXD10 by HIF1α‑AS1 interfered with acetylation, and subsequently resulted in the inhibition of osteoblast differentiation. These results suggested that HIF1α‑AS1 is an essential mediator of osteoblast differentiation, and may thus represent a gene‑therapeutic agent for the treatment of human bone diseases.

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