PMID- 23394201
OWN - NLM
STAT- MEDLINE
DCOM- 20140103
LR  - 20211021
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Print)
IS  - 1937-3341 (Linking)
VI  - 19
IP  - 13-14
DP  - 2013 Jul
TI  - Osteogenic differentiation of adipose-derived stem cells is hypoxia-inducible 
      factor-1 independent.
PG  - 1583-91
LID - 10.1089/ten.TEA.2012.0378 [doi]
AB  - Tissue engineering is a promising approach to repair critical-size defects in 
      bone. Damage to vasculature at the defect site can create a lower O2 environment 
      compared with healthy bone. Local O2 levels influence stem cell behavior, as O2 
      is not only a nutrient, but also a signaling molecule. The hypoxia-inducible 
      factor-1 (HIF-1) is a transcription factor that regulates a wide range of 
      O2-related genes and its contribution in bone repair/formation is an important 
      area that can be exploited. In this study, we examined the effect of low O2 
      environments (1% and 2% O2) on the osteogenic differentiation of adipose-derived 
      stem cells in both two-dimensional (2-D) and three-dimensional (3-D) culture 
      systems. To determine the role of HIF-1 in the differentiation process, an 
      inhibitor was used to block the HIF-1 activity. The samples were examined for 
      osteogenesis markers as measured by quantification of the alkaline phosphatase 
      (ALP) activity, mineral deposition, and expression of osteonectin (ON) and 
      osteopontin (OPN). Results show a downregulation of the osteogenic markers (ALP 
      activity, mineralization, ON, OPN) in both 1% and 2% O2 when compared to 20% O2 
      in both 2-D and 3-D culture. Vascular endothelial growth factor secretion over 28 
      days was significantly higher in low O2 environments and HIF-1 inhibition reduced 
      this effect. The inhibition of the HIF-1 activity did not have a significant 
      impact on the expression of the osteogenic markers, suggesting HIF-1-independent 
      inhibition of osteogenic differentiation in hypoxic conditions.
FAU - Sahai, Suchit
AU  - Sahai S
AD  - Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, 
      USA.
FAU - Williams, Amanda
AU  - Williams A
FAU - Skiles, Matthew L
AU  - Skiles ML
FAU - Blanchette, James O
AU  - Blanchette JO
LA  - eng
GR  - R03 AR062816/AR/NIAMS NIH HHS/United States
GR  - P20GM103499/GM/NIGMS NIH HHS/United States
GR  - R03AR062816/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130404
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Osteonectin)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Adipose Tissue/*cytology
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Osteogenesis/physiology
MH  - Osteonectin/metabolism
MH  - Osteopontin/metabolism
MH  - Stem Cells/*cytology
MH  - Tissue Engineering/methods
PMC - PMC3665297
EDAT- 2013/02/12 06:00
MHDA- 2014/01/05 06:00
PMCR- 2014/07/01
CRDT- 2013/02/12 06:00
PHST- 2013/02/12 06:00 [entrez]
PHST- 2013/02/12 06:00 [pubmed]
PHST- 2014/01/05 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - 10.1089/ten.tea.2012.0378 [pii]
AID - 10.1089/ten.TEA.2012.0378 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2013 Jul;19(13-14):1583-91. doi: 10.1089/ten.TEA.2012.0378. 
      Epub 2013 Apr 4.