Smad3 Induces Chondrogenesis through the Activation of SOX9 via CREB-binding Protein/p300 Recruitment
Copyright policy )Smad3 Induces Chondrogenesis through the Activation of SOX9 via CREB-binding Protein/p300 Recruitment
The transcriptional activation by SRY-type high mobility group box 9 (SOX9) and the transforming growth factor beta (TGF-beta) signals are necessary for chondrogenic differentiation. We have previously shown that CREB-binding protein (CBP/p300) act as an important SOX9 co-activator during chondrogenesis. In the present study, we investigated the relationship between TGF-beta-dependent Smad2/3 signaling pathways and the SOX9-CBP/p300 transcriptional complex at the early stage of chondrogenesis. Overexpressed Smad3 strongly induced the primary chondrogenesis of human mesenchymal stem cells. In addition, Smad3 enhanced the transcriptional activity of SOX9 and the expression of alpha1(II) collagen gene (COL2A1), and small interference RNA against Smad3 (si-Smad3) inhibited them. We observed that Smad2/3 associated with Sox9 in a TGF-beta-dependent manner and formed the transcriptional complexes with SOX9 on the enhancer region of COL2A1. Interestingly, the association between Sox9 and CBP/p300 was increased by Smad3 overexpression and was suppressed by si-Smad3. Our findings indicate that Smad3 has a stronger potential to stimulate the SOX9-dependent transcriptional activity by modulating the interaction between SOX9 and CBP/p300, rather than Smad2. This study suggests that the Smad3 pathway presents a key role for the SOX9-dependent transcriptional activation in primary chondrogenesis.
- Japanese Foundation For Cancer Research Japan
- National Center For Child Health and Development Japan
- Scripps Research Institute United States
- National Presto Industries United States
- Japan Science and Technology Agency Japan
Chromatin Immunoprecipitation, Models, Genetic, Blotting, Western, High Mobility Group Proteins, Nuclear Proteins, DNA, CREB-Binding Protein, Immunohistochemistry, Models, Biological, Adenoviridae, DNA-Binding Proteins, Chondrocytes, Enhancer Elements, Genetic, Genes, Reporter, Humans, Immunoprecipitation, Phosphorylation, Luciferases, Collagen Type II, Cells, Cultured
Chromatin Immunoprecipitation, Models, Genetic, Blotting, Western, High Mobility Group Proteins, Nuclear Proteins, DNA, CREB-Binding Protein, Immunohistochemistry, Models, Biological, Adenoviridae, DNA-Binding Proteins, Chondrocytes, Enhancer Elements, Genetic, Genes, Reporter, Humans, Immunoprecipitation, Phosphorylation, Luciferases, Collagen Type II, Cells, Cultured
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).285 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!