PMID- 22296271
OWN - NLM
STAT- MEDLINE
DCOM- 20130123
LR  - 20181201
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 21
IP  - 13
DP  - 2012 Sep 1
TI  - Short-term exposure to tumor necrosis factor-alpha enables human osteoblasts to 
      direct adipose tissue-derived mesenchymal stem cells into osteogenic 
      differentiation.
PG  - 2420-9
LID - 10.1089/scd.2011.0589 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one major inflammatory factor peaking at 
      24 h after bone fracture in response to injury; its role in bone healing is 
      controversial. The aims of this study were to investigate whether the duration of 
      exposure to TNF-alpha is crucial for the initiation of bone regeneration and to 
      determine its underlying mechanism(s). We demonstrated that 24 h of TNF-alpha 
      treatment significantly abrogated osteocalcin gene expression by human primary 
      osteoblasts (HOBs). However, when TNF-alpha was withdrawn after 24 h, bone 
      sialoprotein and osteocalcin gene expression levels in HOBs at day 7 were 
      significantly up-regulated compared with the HOBs without TNF-alpha treatment. In 
      contrast, continuous TNF-alpha treatment down-regulated bone sialoprotein and 
      osteocalcin gene expression. In addition, in an indirect co-culture system, HOBs 
      pretreated with TNF-alpha for 24 h induced significantly greater osteogenic 
      differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) than the 
      HOBs without TNF-alpha treatment. TNF-alpha treatment also promoted endogenous bone 
      morphogenetic protein 2 (BMP-2) production in HOBs, while blocking the BMP-2 
      signaling pathway with Noggin inhibited osteogenic differentiation of ASCs in the 
      co-culture system. Furthermore, activation of the p38 mitogen-activated protein 
      kinase (MAPK) signaling pathway after TNF-alpha treatment occurred earlier than BMP-2 
      protein expression. BMP-2 production by HOBs and osteogenic differentiation of 
      ASCs in the co-culture system with HOBs was significantly decreased when HOBs 
      were pretreated with TNF-alpha in combination with the p38 MAPK-specific inhibitor 
      (SB203580). Taken together, we provide evidence that exposure duration is a 
      critical element in determining TNF-alpha's effects on bone regeneration. We also 
      demonstrate that the p38 MAPK signaling pathway regulates the expression of BMP-2 
      in osteoblasts, which then acts through a paracrine loop, to direct the 
      osteoblast lineage commitment of mesenchymal stem cells.
FAU - Lu, ZuFu
AU  - Lu Z
AD  - Biomaterials and Tissue Engineering Research Unit, School of AMME, The University 
      of Sydney, Sydney, Australia.
FAU - Wang, Guocheng
AU  - Wang G
FAU - Dunstan, Colin R
AU  - Dunstan CR
FAU - Zreiqat, Hala
AU  - Zreiqat H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120306
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (BMP2 protein, human)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Carrier Proteins)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Imidazoles)
RN  - 0 (Integrin-Binding Sialoprotein)
RN  - 0 (Pyridines)
RN  - 0 (RUNX2 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 104982-03-8 (Osteocalcin)
RN  - 148294-77-3 (noggin protein)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Adipose Tissue/*cytology
MH  - Adolescent
MH  - Bone Morphogenetic Protein 2/antagonists & inhibitors/genetics/metabolism
MH  - Bone Regeneration
MH  - Carrier Proteins/pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation
MH  - Child
MH  - Coculture Techniques
MH  - Core Binding Factor Alpha 1 Subunit/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Integrin-Binding Sialoprotein/genetics/metabolism
MH  - MAP Kinase Signaling System
MH  - Mesenchymal Stem Cells/*cytology/drug effects
MH  - Osteoblasts/*cytology/drug effects/metabolism
MH  - Osteocalcin/genetics/metabolism
MH  - *Osteogenesis
MH  - Pyridines/pharmacology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Young Adult
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
EDAT- 2012/02/03 06:00
MHDA- 2013/01/24 06:00
CRDT- 2012/02/03 06:00
PHST- 2012/02/03 06:00 [entrez]
PHST- 2012/02/03 06:00 [pubmed]
PHST- 2013/01/24 06:00 [medline]
AID - 10.1089/scd.2011.0589 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2012 Sep 1;21(13):2420-9. doi: 10.1089/scd.2011.0589. Epub 2012 
      Mar 6.