PMID- 30847950
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20210109
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 10
DP  - 2019 Aug
TI  - ELP2 negatively regulates osteoblastic differentiation impaired by tumor necrosis 
      factor alpha in MC3T3-E1 cells through STAT3 activation.
PG  - 18075-18085
LID - 10.1002/jcp.28440 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pluripotent signaling molecule. The 
      biological effect of TNF-alpha includes slowing down osteogenic differentiation, 
      which can lead to bone dysplasia in long-term inflammatory microenvironments. 
      Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 
      (StIP1, also known as elongator complex protein 2, ELP2) play a role in 
      inhibiting TNF-alpha-induced osteoblast differentiation. In the present study, we 
      investigated whether and how ELP2 activation mediates the effects of TNF-alpha on 
      osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic 
      MC3T3-E1 cells, we found that TNF-alpha inhibited osteoblastic differentiation 
      accompanied by an increase in ELP2 expression and STAT3 activation. Forced ELP2 
      expression inhibited osteogenic differentiation of MC3T3-E1 cells, with a 
      decrease in the expression of osteoblast marker genes, alkaline phosphatase 
      activity, and matrix mineralization capacity. In contrast, ELP2 silencing 
      ameliorated osteogenic differentiation in MC3T3-E1 cells, even after TNF-alpha 
      stimulation. The TNF-alpha-induced inhibitory effect on osteoblastic differentiation 
      was therefore mediated by ELP2, which was associated with Janus kinase 2 
      (JAK2)/STAT3 activation. These results suggest that ELP2 is upregulated at the 
      differentiation of MC3T3-E1 cells into osteoblasts and inhibits osteogenic 
      differentiation in response to TNF-alpha through STAT3 activation.
CI  - (c) 2019 The Authors. Journal of Cellular Physiology Published by Wiley 
      Periodicals, Inc.
FAU - Xu, Chang-Peng
AU  - Xu CP
AUID- ORCID: 0000-0001-6349-0842
AD  - Department of Orthopaedics, Guangdong Second Provincial General Hospital, 
      Guangzhou, Guangdong, People's Republic of China.
FAU - Sun, Hong-Tao
AU  - Sun HT
AD  - Department of Orthopaedics, Guangdong Second Provincial General Hospital, 
      Guangzhou, Guangdong, People's Republic of China.
FAU - Yang, Ya-Jun
AU  - Yang YJ
AD  - Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong, 
      People's Republic of China.
FAU - Cui, Zhuang
AU  - Cui Z
AD  - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Orthopaedics, The Inner Mongolia People's Hospital, Hohhot, Inner 
      Mongolia, People's Republic of China.
FAU - Yu, Bin
AU  - Yu B
AD  - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Wang, Fa-Zheng
AU  - Wang FZ
AD  - Department of Orthopaedics, The First People's Hospital of Kashgar Prefecture, 
      Kashgar, Xinjiang, People's Republic of China.
FAU - Yang, Qing-Po
AU  - Yang QP
AD  - Department of Orthopaedics, The First People's Hospital of Kashgar Prefecture, 
      Kashgar, Xinjiang, People's Republic of China.
FAU - Qi, Yong
AU  - Qi Y
AD  - Department of Orthopaedics, Guangdong Second Provincial General Hospital, 
      Guangzhou, Guangdong, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190307
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (ELP2 protein, human)
RN  - 0 (Elp2 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Differentiation/*drug effects
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Janus Kinase 2/metabolism
MH  - Mice
MH  - Osteoblasts/*drug effects/metabolism
MH  - Osteogenesis/*drug effects
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC6618314
OTO - NOTNLM
OT  - ELP2
OT  - osteoblastic differentiation
OT  - signal transducer and activator of transcription 3
OT  - tumor necrosis factor-alpha
COIS- The authors declare that there are no conflict of interests.
EDAT- 2019/03/09 06:00
MHDA- 2020/05/27 06:00
PMCR- 2019/07/10
CRDT- 2019/03/09 06:00
PHST- 2018/08/29 00:00 [received]
PHST- 2019/02/09 00:00 [revised]
PHST- 2019/02/14 00:00 [accepted]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/07/10 00:00 [pmc-release]
AID - JCP28440 [pii]
AID - 10.1002/jcp.28440 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Aug;234(10):18075-18085. doi: 10.1002/jcp.28440. Epub 2019 
      Mar 7.