RRC ID 56124
Author Misawa A, Orimo H.
Title lncRNA HOTAIR Inhibits Mineralization in Osteoblastic Osteosarcoma Cells by Epigenetically Repressing ALPL.
Journal Calcif Tissue Int
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.
Volume 103(4)
Pages 422-430
Published 2018-10-1
DOI 10.1007/s00223-018-0434-0
PII 10.1007/s00223-018-0434-0
PMID 29846771
MeSH Alkaline Phosphatase / biosynthesis* Alkaline Phosphatase / genetics Calcification, Physiologic / physiology* Cell Line, Tumor DNA Methylation Epigenesis, Genetic Gene Expression Regulation / physiology* Gene Knockdown Techniques Humans Osteoblasts / metabolism* Osteosarcoma RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism*
IF 3.265
Times Cited 2
Human and Animal Cells Saos-2(RCB0428)