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p38 MAP Kinase Regulation of AP-2 Binding in TGF-β1-Stimulated Chondrogenesis of Human Trabecular Bone-Derived Cells
- Source :
- Annals of the New York Academy of Sciences. 961:172-177
- Publication Year :
- 2002
- Publisher :
- Wiley, 2002.
-
Abstract
- Collagenase-treated, explanted human trabecular-bone chips are an excellent source of osteoblast-like cells. We have recently shown the multiple differentiation potential of these cells; in addition to osteogenesis and adipogenesis, these cells also undergo chondrogenesis when maintained as high-density pellet cultures (250,000 cells/pellet) in a serum-free, chemically defined medium stimulated with TGF-beta1 (10 ng/mL). In this investigation, we have analyzed how transactivating nuclear transcription factors, specifically AP-2 and SP-1, may interact with common cis-acting elements found in the regulatory region of cartilage-specific genes as part of the signal transduction mechanism of TGF-beta1 and p38 during chondrogenesis of human trabecular bone-derived multipotential cells. Both TGF-beta1 stimulation and p38 MAP kinase activation affect the binding of AP-2 as well as SP-1 to oligonucleotides with sequence similarity to the overlapping AP-2/SP-1 sites found in the putative 52-bp immediate upstream regulatory region and the 5'-untranslated region of the human aggrecan gene. Electrophoretic mobility shift assays show that TGF-beta1 treatment of the bone-derived cells inhibits AP-2 DNA binding but enhances the DNA binding ability of SP-1. Additionally, treatment of these TGF-beta1-stimulated cells with p38 MAP kinase inhibitor, SB203580, rescued the AP-2 DNA binding but did not affect SP-1 DNA binding. These findings indicate that AP-2 DNA binding is the target of both TGF-beta1 and p38 MAP kinase signaling pathways and suggest a possible signal transduction cascade whereby TGF-beta1 induction of chondrogenesis involves the activation of p38 MAP kinase and the subsequent inhibition of DNA binding by AP-2, thereby preventing the transcriptional repression of the aggrecan gene.
- Subjects :
- Pyridines
Sp1 Transcription Factor
MAPK7
Biology
p38 Mitogen-Activated Protein Kinases
Bone and Bones
General Biochemistry, Genetics and Molecular Biology
MAP2K7
Mesoderm
Transforming Growth Factor beta1
Chondrocytes
History and Philosophy of Science
Transforming Growth Factor beta
MAP2K1
Humans
Enzyme Inhibitors
Transcription factor
MAPK14
Cell Nucleus
Bone Development
Reverse Transcriptase Polymerase Chain Reaction
Oligonucleotide
General Neuroscience
Imidazoles
Cell Differentiation
Chondrogenesis
Molecular biology
DNA-Binding Proteins
Enzyme Activation
Transcription Factor AP-2
RNA
Mitogen-Activated Protein Kinases
Signal transduction
Cell Division
Transcription Factors
Subjects
Details
- ISSN :
- 17496632 and 00778923
- Volume :
- 961
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....587e0528465f24b0eb4d85c659db0e7a