The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts.

Nature Metabolism
Yao SunXiaogang Wang

Abstract

Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.

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Jul 7, 2020·Biochemical Society Transactions·Zi ZouCijun Shuai
Dec 31, 2020·Acta Biochimica Et Biophysica Sinica·Zhen ZhangWei Hong
Jan 2, 2021·Frontiers in Cell and Developmental Biology·Qian LiuGuangwei Wang
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Jun 5, 2021·Nature Communications·Fujun JinXiaogang Wang
Jun 24, 2021·Journal of Dental Research·J LiY Sun

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Methods Mentioned

BETA
PCR
RNA-seq
pulldown
immunoprecipitation
RIP
ChIP
total hip arthroplasty
electrophoresis
transfection
genotyping

Software Mentioned

EdgeR
SPSS
UCSC Genome Browser
DAVID Bioinformatics Resources
ImageJ
Ensembl Genome Browser
Ensembl
blast

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