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lncRNA HOTAIR Inhibits Mineralization in Osteoblastic Osteosarcoma Cells by Epigenetically Repressing ALPL

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Abstract

HOTAIR is a lncRNA that plays critical role in gene regulation and chromatin dynamics through epigenetic mechanisms. In this work we studied the physiological role of HOTAIR during the process of mineralization using osteoblastic osteosarcoma cells focusing in ALPL (Tissue Non-Specific Alkaline Phosphatase), a pivotal gene that controls bone formation. HOTAIR knockdown resulted in upregulation of ALPL, increase of alkaline phosphatase (ALP) activity, and enhanced mineralization in osteoblastic SaOS-2 cells cultured in mineralizing medium. Luciferase assays using reporter vectors containing ALPL promoter showed that HOTAIR repression increases ALPL promoter activity. Furthermore, HOTAIR knockdown increased histone H3K4 methylation levels at ALPL promoter region, suggesting that ALPL repression by HOTAIR is regulated by epigenetic mechanisms. This work supports that physiological bone formation is epigenetically regulated by a lncRNA.

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Acknowledgements

We are grateful to T. Takizawa and T. Kosuge from the Department of Molecular Medicine and Anatomy, Nippon Medical School, for technical support for Luciferase and ChIP assays. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A.M.) KAKENHI Grant Number: 16K18411.

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  1. Division of Metabolism and Nutrition, Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8602, Japan

    Aya Misawa & Hideo Orimo

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  1. Aya Misawa
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  2. Hideo Orimo
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Correspondence to Hideo Orimo.

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Misawa, A., Orimo, H. lncRNA HOTAIR Inhibits Mineralization in Osteoblastic Osteosarcoma Cells by Epigenetically Repressing ALPL. Calcif Tissue Int 103, 422–430 (2018). https://doi.org/10.1007/s00223-018-0434-0

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