Division of Metabolism and Nutrition, Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8602, Japan.
Calcif Tissue Int. 2018 Oct;103(4):422-430. doi: 10.1007/s00223-018-0434-0. Epub 2018 May 30.
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.
HOTAIR 是一种长链非编码 RNA，通过表观遗传机制在基因调控和染色质动力学中发挥关键作用。在这项工作中，我们使用成骨肉瘤细胞研究了 HOTAIR 在矿化过程中的生理作用，重点研究了控制骨形成的关键基因 ALPL（组织非特异性碱性磷酸酶）。HOTAIR 敲低导致 ALPL 上调，碱性磷酸酶 (ALP) 活性增加，并增强矿化在矿化培养基中培养的成骨细胞 SaOS-2 细胞。使用包含 ALPL 启动子的报告载体进行的荧光素酶测定表明，HOTAIR 抑制增加了 ALPL 启动子活性。此外，HOTAIR 敲低增加了 ALPL 启动子区域的组蛋白 H3K4 甲基化水平，表明 HOTAIR 对 ALPL 的抑制受表观遗传机制调控。这项工作支持生理骨形成受长链非编码 RNA 的表观遗传调控。
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