Back to Search
Start Over
Suppression of PPAR Transactivation Switches Cell Fate of Bone Marrow Stem Cells from Adipocytes into Osteoblasts
- Source :
- Annals of the New York Academy of Sciences. 1116:182-195
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- Osteoblasts and adipocytes differentiate from common pleiotropic mesenchymal stem cells under transcriptional controls by numerous factors and multiple intracellular signalings. However, cellular signaling factors that determine cell fates of mensenchymal stem cells in bone marrow remain to be largely uncovered, though peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is well established as a prime inducer of adipogenesis. Here, we describe two signaling pathways that induce the cell fate decision into osteoblasts from adipocytes. One signaling is a TAK1/TAB1/NIK cascade activated by TNF-alpha and IL-1, and the activated NF-kappaB blocked the DNA binding of PPAR-gamma, attenuating the activated PPAR-mediated adipogenesis. The second signaling is the noncanonical Wnt pathway through CaMKII-TAK1/TAB2-NLK. Activated NLK by a noncanonical Wnt ligand (Wnt-5a) transrepresses PPAR transactivation through a histone methyltransferase, SETDB1. Wnt-5a induces phosphorylation of NLK, leading to the formation of a corepressor complex that inactivates PPAR function through histone H3-K9 methylation. Thus, two signaling pathways lead to an osteoblastic cell lineage decision from mesenchymal stem cells through two distinct modes of PPAR transrepression.
- Subjects :
- Transcriptional Activation
Cell signaling
Osteoblasts
General Neuroscience
Cellular differentiation
Peroxisome Proliferator-Activated Receptors
Mesenchymal stem cell
Wnt signaling pathway
Cell Differentiation
Histone-Lysine N-Methyltransferase
Biology
Hematopoietic Stem Cells
General Biochemistry, Genetics and Molecular Biology
Transactivation
History and Philosophy of Science
Adipogenesis
Adipocytes
Histone Methyltransferases
Cancer research
Animals
Cell Lineage
Protein Methyltransferases
Stem cell
Transrepression
Subjects
Details
- ISSN :
- 00778923
- Volume :
- 1116
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....794dbc0270efa9a78e9e6302b21a7b49