PMID- 31827076
OWN - NLM
STAT- MEDLINE
DCOM- 20200911
LR  - 20231213
IS  - 2041-4889 (Electronic)
VI  - 10
IP  - 12
DP  - 2019 Dec 11
TI  - LncRNA ODIR1 inhibits osteogenic differentiation of hUC-MSCs through the 
      FBXO25/H2BK120ub/H3K4me3/OSX axis.
PG  - 947
LID - 10.1038/s41419-019-2148-2 [doi]
LID - 947
AB  - Long noncoding RNAs (lncRNAs) have been demonstrated to be important regulators 
      during the osteogenic differentiation of mesenchymal stem cells (MSCs). We 
      analyzed the lncRNA expression profile during osteogenic differentiation of human 
      umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and identified a 
      significantly downregulated lncRNA RP11-527N22.2, named osteogenic 
      differentiation inhibitory lncRNA 1, ODIR1. In hUC-MSCs, ODIR1 knockdown 
      significantly promoted osteogenic differentiation, whereas overexpression 
      inhibited osteogenic differentiation in vitro and in vivo. Mechanistically, ODIR1 
      interacts with F-box protein 25 (FBXO25) and facilitates the proteasome-dependent 
      degradation of FBXO25 by recruiting Cullin 3 (CUL3). FBXO25 increases the 
      mono-ubiquitination of H2BK120 (H2BK120ub) which subsequently promotes the 
      trimethylation of H3K4 (H3K4me3). Both H2BK120ub and H3K4me3 form a loose 
      chromatin structure, inducing the transcription of the key transcription factor 
      osterix (OSX) and increasing the expression of the downstream osteoblast markers, 
      osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP). In summary, 
      ODIR1 acts as a key negative regulator during the osteogenic differentiation of 
      hUC-MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis, which may provide a novel 
      understanding of lncRNAs that regulate the osteogenesis of MSCs and a potential 
      therapeutic strategy for the regeneration of bone defects.
FAU - He, Shiwei
AU  - He S
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
AD  - The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry 
      of Education, Cancer Research Institute and School of Basic Medical Sciences, 
      Central South University, Changsha, 410078, China.
AD  - Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Disease Genome 
      Research Center, the Third Xiangya Hospital, Central South University, Changsha, 
      410013, China.
FAU - Yang, Sheng
AU  - Yang S
AD  - Department of Obstetrics and Gynecology, General Hospital, Shenzhen University, 
      Shenzhen, 518053, China.
FAU - Zhang, Yanru
AU  - Zhang Y
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Li, Xiaoling
AU  - Li X
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Gao, Dan
AU  - Gao D
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Zhong, Yancheng
AU  - Zhong Y
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Cao, Lihua
AU  - Cao L
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Ma, Haotian
AU  - Ma H
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Liu, Ying
AU  - Liu Y
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Li, Guiyuan
AU  - Li G
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China.
FAU - Peng, Shuping
AU  - Peng S
AD  - NHC Key Laboratory of Carcinogenesis, Hunan Provincial Tumor Hospital, Central 
      South University, Changsha, 410013, China. shuping@csu.edu.cn.
AD  - The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry 
      of Education, Cancer Research Institute and School of Basic Medical Sciences, 
      Central South University, Changsha, 410078, China. shuping@csu.edu.cn.
AD  - Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Disease Genome 
      Research Center, the Third Xiangya Hospital, Central South University, Changsha, 
      410013, China. shuping@csu.edu.cn.
FAU - Shuai, Cijun
AU  - Shuai C
AD  - Jiangxi University of Science and Technology, Ganzhou, 341000, China. 
      shuai@csu.edu.cn.
AD  - State Key Laboratory of High Performance Complex Manufacturing, Central South 
      University, Changsha, 410083, China. shuai@csu.edu.cn.
LA  - eng
GR  - 81871494/National Natural Science Foundation of China (National Science 
      Foundation of China)/International
GR  - 81572577/National Natural Science Foundation of China (National Science 
      Foundation of China)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191211
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (F-Box Proteins)
RN  - 0 (FBXO25 protein, human)
RN  - 0 (Histones)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Sp7 Transcription Factor)
RN  - 0 (SP7 protein, human)
RN  - 0 (histone H3 trimethyl Lys4)
RN  - 104982-03-8 (Osteocalcin)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Cell Differentiation/genetics
MH  - Cells, Cultured
MH  - F-Box Proteins/*genetics
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Histones/*genetics
MH  - Humans
MH  - Mesenchymal Stem Cells/cytology
MH  - Nerve Tissue Proteins/*genetics
MH  - Osteoblasts/metabolism
MH  - Osteocalcin/genetics
MH  - Osteogenesis/*genetics
MH  - Osteopontin/genetics
MH  - RNA, Long Noncoding/*genetics
MH  - Signal Transduction/genetics
MH  - Sp7 Transcription Factor/*genetics
MH  - Umbilical Cord/cytology
PMC - PMC6906393
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/12/13 06:00
MHDA- 2020/09/12 06:00
PMCR- 2019/12/11
CRDT- 2019/12/13 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2019/11/11 00:00 [accepted]
PHST- 2019/11/01 00:00 [revised]
PHST- 2019/12/13 06:00 [entrez]
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/12/11 00:00 [pmc-release]
AID - 10.1038/s41419-019-2148-2 [pii]
AID - 2148 [pii]
AID - 10.1038/s41419-019-2148-2 [doi]
PST - epublish
SO  - Cell Death Dis. 2019 Dec 11;10(12):947. doi: 10.1038/s41419-019-2148-2.