Inhibition of histone deacetylase activity in reduced oxygen environment enhances the osteogenesis of mouse adipose-derived stromal cells

Yue Xu, Kyle E. Hammerick, Aaron James, Antoine L. Carre, Philipp Leucht, Amato J. Giaccia, Michael T. Longaker

Research output: Contribution to journalArticle

Abstract

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% O2). Conversely, adipogenesis was decreased with treatments of NaB or VPA at all oxygen tensions. Finally, NaB-or VPA-treated, reduced oxygen tension-exposed (1% O2) 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.

Original languageEnglish (US)
Pages (from-to)3697-3707
Number of pages11
JournalTissue Engineering - Part A
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

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Histone Deacetylases
Stromal Cells
Osteogenesis
Oxygen
Valproic Acid
Histone Deacetylase Inhibitors
Acids
Adipogenesis
Bone Regeneration
Butyric Acid
Cell proliferation
Adipose Tissue
Regeneration
Bone
Sodium
Cell Proliferation
Tissue
Defects

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Inhibition of histone deacetylase activity in reduced oxygen environment enhances the osteogenesis of mouse adipose-derived stromal cells. / Xu, Yue; Hammerick, Kyle E.; James, Aaron; Carre, Antoine L.; Leucht, Philipp; Giaccia, Amato J.; Longaker, Michael T.

In: Tissue Engineering - Part A, Vol. 15, No. 12, 01.12.2009, p. 3697-3707.

Research output: Contribution to journalArticle

Xu, Yue ; Hammerick, Kyle E. ; James, Aaron ; Carre, Antoine L. ; Leucht, Philipp ; Giaccia, Amato J. ; Longaker, Michael T. / Inhibition of histone deacetylase activity in reduced oxygen environment enhances the osteogenesis of mouse adipose-derived stromal cells. In: Tissue Engineering - Part A. 2009 ; Vol. 15, No. 12. pp. 3697-3707.
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