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PPAR Research
Volume 2010, Article ID 341671, 6 pages
Review Article

PPAR- Signaling Crosstalk in Mesenchymal Stem Cells

1Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
2College of Science & General Studies, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
3Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan

Received 30 April 2010; Accepted 25 June 2010

Academic Editor: Yaacov Barak

Copyright © 2010 Ichiro Takada et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peroxisome proliferator-activated receptor-gamma (PPAR- ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR- acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF- , TGF- ) had been known to inhibit adipocyte differentiation in mesenchymal stem cells (MSCs), we examined the effect of these cytokines on the transactivation function of PPAR- . We found that the TNF- /IL-1-activated TAK1/TAB1/NIK (NF B-inducible kinase) signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR- by blocking the receptor binding to the cognate DNA response elements. Furthermore, it has been shown that the noncanonical Wnts are expressed in MSCs and that Wnt-5a was capable to inhibit transactivation by PPAR- . Treatment with Wnt5a-activated NLK (nemo-like kinase) induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1) protein complexes with PPAR- . This resulted in histoneH3K9 tri-methylation at PPAR- target gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR- regulatory function in its target cells and tissues.