title: 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.
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.
authors.affiliation: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C000610087:long non-coding RNA HIF 1alpha-anti-sense 1, human; C072064:HOXD10 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1