PMID- 22396737
OWN - NLM
STAT- MEDLINE
DCOM- 20120723
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 3
DP  - 2012
TI  - Glucocorticoid-induced leucine zipper (GILZ) antagonizes TNF-alpha inhibition of 
      mesenchymal stem cell osteogenic differentiation.
PG  - e31717
LID - 10.1371/journal.pone.0031717 [doi]
LID - e31717
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine that 
      inhibits osteoblast differentiation while stimulating osteoclast differentiation 
      and bone resorption. TNF-alpha activates MAP kinase pathway leading to inhibition of 
      osterix (Osx) expression. TNF-alpha also induces the expression of E3 ubiquitin 
      ligase protein Smurf1 and Smurf2 and promotes degradation of Runx2, another key 
      transcription factor regulating osteoblast differentiation and bone formation. We 
      showed previously that overexpression of glucocorticoid (GC)-induced leucine 
      zipper (GILZ) enhances osteogenic differentiation of bone marrow mesenchymal stem 
      cells (MSCs). We and others also showed that GILZ is a GC effecter and mediates 
      GC anti-inflammatory activity. In this study, we asked the question whether GILZ 
      retains its osteogenic activity while functioning as an anti-inflammatory 
      mediator. To address this question, we infected mouse bone marrow MSCs with 
      retroviruses expressing GILZ and induced them for osteogenic differentiation in 
      the presence or absence of TNF-alpha. Our results show that overexpression of GILZ 
      antagonized the inhibitory effects of TNF-alpha on MSC osteogenic differentiation and 
      the mRNA and protein expression of Osx and Runx2, two pivotal osteogenic 
      regulators. Further studies show that these antagonistic actions occur via 
      mechanisms involving GILZ inhibition of TNF-alpha-induced ERK MAP kinase activation 
      and protein degradation. These results suggest that GILZ may have therapeutic 
      potential as a novel anti-inflammation therapy.
FAU - He, Linlin
AU  - He L
AD  - Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, 
      Augusta, Georgia, United States of America.
FAU - Yang, Nianlan
AU  - Yang N
FAU - Isales, Carlos M
AU  - Isales CM
FAU - Shi, Xing-Ming
AU  - Shi XM
LA  - eng
GR  - P01 AG036675/AG/NIA NIH HHS/United States
GR  - R01 DK076045/DK/NIDDK NIH HHS/United States
GR  - P01AG036675/AG/NIA NIH HHS/United States
GR  - DK76045/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120302
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Dsip1 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glucocorticoids)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Differentiation
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Glucocorticoids/*metabolism
MH  - Inflammation
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteogenesis
MH  - Phosphorylation
MH  - Transcription Factors/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC3292550
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/03/08 06:00
MHDA- 2012/07/24 06:00
PMCR- 2012/03/02
CRDT- 2012/03/08 06:00
PHST- 2011/06/14 00:00 [received]
PHST- 2012/01/18 00:00 [accepted]
PHST- 2012/03/08 06:00 [entrez]
PHST- 2012/03/08 06:00 [pubmed]
PHST- 2012/07/24 06:00 [medline]
PHST- 2012/03/02 00:00 [pmc-release]
AID - PONE-D-11-10793 [pii]
AID - 10.1371/journal.pone.0031717 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(3):e31717. doi: 10.1371/journal.pone.0031717. Epub 2012 Mar 2.