Biochem Biophys Res Commun. 2007 Apr 20;355(4):913-8. Epub 2007 Feb 21.

Sodium butyrate activates ERK to regulate differentiation of mesenchymal
stem cells.

Chen TH, Chen WM, Hsu KH, Kuo CD, Hung SC.

Orthopaedics and Traumatology, Veterans General Hospital, Taipei,
Taiwan.

Histone deacetylase inhibitors such as sodium butyrate are known to
regulate the differentiation of a variety of cells. Mesenchymal stem
cells (MSCs) differentiate into osteoblasts and adipocytes under
transcriptional control of Runx2 and PPARgamma2, respectively. How these
two transcription factors are regulated by sodium butyrate in order to
specify the alternate cell fates remains a pivotal question. Sodium
butyrate stimulated osteogenic differentiation and increased expression
of Runx2 and genes regulated by Runx2 when cells were induced to undergo
osteogenic differentiation. Sodium butyrate suppressed the adipogenic
differentiation and decreased the expression of PPARgamma2 and LPL when
MSCs were treated under conditions that promote adipogenic
differentiation. Sodium butyrate also decreased the ratio of RANKL/OPG
gene expression by MSCs. Analysis of MSCs induced in the presence of
sodium butyrate revealed an immediate increase in ERK phosphorylation by
sodium butyrate. The MEK-specific inhibitor, PD98059 but not p38- or
JNK-specific inhibitor and the transfection with dominant negative ERK
expressing plasmids blocked the sodium butyrate-induced regulation of
MSC differentiation and increase in the RANKL/OPG ratio. Our results
suggest that sodium butyrate modulates MSC differentiation and the
RANKL/OPG ratio via activating ERK, and could be applied for in vivo
bone growth using MSCs.

Publication Types:

*  Research Support, Non-U.S. Gov't

PMID: 17331472 [PubMed - indexed for MEDLINE]