Document Detail


Inhibition of histone deacetylase activity in reduced oxygen environment enhances the osteogenesis of mouse adipose-derived stromal cells.
MedLine Citation:
PMID:  19505250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies suggest that oxygen tension has a great impact on the osteogenic differentiation capacity of mesenchymal cells derived from adipose tissue: reduced oxygen impedes osteogenesis. We have found that expansion of mouse adipose-derived stromal cells (mASCs) in reduced oxygen tension (10%) results in increased cell proliferation along with induction of histone deacetylase (HDAC) activity. In this study, we utilized two HDAC inhibitors (HDACi), sodium butyrate (NaB) and valproic acid (VPA), and studied their effects on mASCs expanded in various oxygen tensions (21%, 10%, and 1% O(2)). Significant growth inhibition was observed with NaB or VPA treatment in each oxygen tension. Osteogenesis was enhanced by treatment with NaB or VPA, particularly in reduced oxygen tensions (10% and 1% O(2)). Conversely, adipogenesis was decreased with treatments of NaB or VPA at all oxygen tensions. Finally, NaB- or VPA-treated, reduced oxygen tension-exposed (1% O(2)) ASCs were grafted into surgically created mouse tibial defects and resulted in significantly increased bone regeneration. In conclusion, HDACi significantly promote the osteogenic differentiation of mASCs exposed to reduced oxygen tension; HDACi may hold promise for future clinical applications of ASCs for skeletal regeneration.
Authors:
Yue Xu; Kyle E Hammerick; Aaron W James; Antoine L Carre; Philipp Leucht; Amato J Giaccia; Michael T Longaker
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  15     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-09     Completed Date:  2010-02-03     Revised Date:  2011-03-03    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3697-707     Citation Subset:  IM    
Affiliation:
Plastic and Reconstructive Surgery Division, Hagey Pediatric Regenerative Research Laboratory, Department of Surgery, Stanford University School of Medicine, Stanford University, Stanford, California 94305-5148, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipogenesis / drug effects
Adipose Tissue / cytology*
Alkaline Phosphatase / metabolism
Animals
Bromodeoxyuridine / metabolism
Butyrates / pharmacology
Cell Proliferation / drug effects
Gene Expression Regulation / drug effects
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism*
Mice
Osteogenesis / drug effects*,  genetics
Oxygen / analysis*
Stromal Cells / cytology*,  drug effects,  enzymology*,  transplantation
Tibia / drug effects,  pathology
Valproic Acid / pharmacology
Grant Support
ID/Acronym/Agency:
R01 DE-13194/DE/NIDCR NIH HHS; R01 DE-14526/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Butyrates; 0/Histone Deacetylase Inhibitors; 59-14-3/Bromodeoxyuridine; 7782-44-7/Oxygen; 99-66-1/Valproic Acid; EC 3.1.3.1/Alkaline Phosphatase; EC 3.5.1.98/Histone Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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