PMID- 27401008
OWN - NLM
STAT- MEDLINE
DCOM- 20170307
LR  - 20181202
IS  - 1543-706X (Electronic)
IS  - 1071-2690 (Linking)
VI  - 52
IP  - 10
DP  - 2016 Dec
TI  - Inhibition of Runx2 signaling by TNF-alpha in ST2 murine bone marrow stromal cells 
      undergoing osteogenic differentiation.
PG  - 1026-1033
AB  - Tumor necrosis factor-alpha (TNF-alpha) inhibits osteogenic differentiation of murine 
      bone marrow stromal cells, and transcription factor Runx2 serves as an essential 
      regulation target in the process. The underlying mechanism may involve the 
      regulation of Runx2 expression and the Runx2 activity in downstream gene 
      transcription, which has not been fully elucidated. In this study, ST2 murine 
      bone marrow-derived stromal cells were treated with bone morphogenetic protein-2 
      (BMP-2) and/or TNF-alpha in osteogenic medium, and the expression of Runx2 was 
      estimated. Cells were transfected with Runx2, p65, inhibitor of kappaBalpha (IkappaBalpha), 
      9.0 kb bone sialoprotein (BSP) promoter-luciferase or osteoblast-specific 
      cis-acting element 2 (OSE2)-luciferase reporter vectors, and then real time-PCR 
      and dual luciferase analysis were used to investigate the effect of TNF-alpha on 
      Runx2-activated osteogenic gene transcription and the molecular mechanism. We 
      found that TNF-alpha inhibited BMP-2-induced osteogenic marker expression and both 
      the spontaneous and BMP-2-induced Runx2 expression. TNF-alpha stimulation or 
      overexpression of nuclear factor-kappa B (NF-kappaB) p65 subunit repressed the 
      Runx2-activated BSP and osteocalcin (OC) transcriptions. The Runx2-induced 9.0 kb 
      BSP promoter activity was attenuated by TNF-alpha or p65, while the OSE2 activity was 
      not affected. Besides, blockage of NF-kappaB by IkappaBalpha overexpression eliminated these 
      inhibitory effects of TNF-alpha on Runx2 signaling. These results suggest that in 
      murine bone marrow stromal cells undergoing osteogenic differentiation, TNF-alpha and 
      it activated NF-kappaB pathway inhibit the expression of Runx2 gene, and suppress the 
      Runx2-mediated osteogenic gene transcription via the 9.0 kb BSP promoter.
FAU - Ye, Xin
AU  - Ye X
AD  - School of Stomatology, Shandong University, 44-1 West Wen Hua Road, Jinan, 
      Shandong Province, 250012, China.
AD  - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong 
      University, Jinan, China.
FAU - Huang, Haiyun
AU  - Huang H
AD  - School of Stomatology, Shandong University, 44-1 West Wen Hua Road, Jinan, 
      Shandong Province, 250012, China.
AD  - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong 
      University, Jinan, China.
FAU - Zhao, Ning
AU  - Zhao N
AD  - School of Stomatology, Shandong University, 44-1 West Wen Hua Road, Jinan, 
      Shandong Province, 250012, China.
AD  - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong 
      University, Jinan, China.
FAU - Zhang, Jin
AU  - Zhang J
AD  - School of Stomatology, Shandong University, 44-1 West Wen Hua Road, Jinan, 
      Shandong Province, 250012, China. tendenzj@sdu.edu.cn.
AD  - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong 
      University, Jinan, China. tendenzj@sdu.edu.cn.
FAU - Yang, Pishan
AU  - Yang P
AD  - School of Stomatology, Shandong University, 44-1 West Wen Hua Road, Jinan, 
      Shandong Province, 250012, China. yangps@sdu.edu.cn.
AD  - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong 
      University, Jinan, China. yangps@sdu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160711
PL  - Germany
TA  - In Vitro Cell Dev Biol Anim
JT  - In vitro cellular & developmental biology. Animal
JID - 9418515
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Integrin-Binding Sialoprotein)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Base Pairing/genetics
MH  - Bone Morphogenetic Protein 2/pharmacology
MH  - Cell Differentiation/*drug effects/genetics
MH  - Cell Line
MH  - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Integrin-Binding Sialoprotein/genetics
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Osteogenesis/*drug effects/genetics
MH  - Promoter Regions, Genetic
MH  - Signal Transduction/*drug effects
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
OTO - NOTNLM
OT  - Bone marrow stromal cells
OT  - NF-kappaB
OT  - Osteogenic differentiation
OT  - Runx2
OT  - Tumor necrosis factor-alpha
EDAT- 2016/07/13 06:00
MHDA- 2017/03/08 06:00
CRDT- 2016/07/13 06:00
PHST- 2016/04/09 00:00 [received]
PHST- 2016/06/22 00:00 [accepted]
PHST- 2016/07/13 06:00 [pubmed]
PHST- 2017/03/08 06:00 [medline]
PHST- 2016/07/13 06:00 [entrez]
AID - 10.1007/s11626-016-0068-3 [pii]
AID - 10.1007/s11626-016-0068-3 [doi]
PST - ppublish
SO  - In Vitro Cell Dev Biol Anim. 2016 Dec;52(10):1026-1033. doi: 
      10.1007/s11626-016-0068-3. Epub 2016 Jul 11.