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Rac1 signaling stimulates N-cadherin expression, mesenchymal condensation, and chondrogenesis.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Aug 10; Vol. 282 (32), pp. 23500-8. Date of Electronic Publication: 2007 Jun 14. - Publication Year :
- 2007
-
Abstract
- The molecular mechanisms controlling differentiation of mesenchymal precursor cells into chondrocytes (chondrogenesis) are not completely understood. We have recently shown that the small GTPase RhoA inhibits this process. Here we demonstrate that a different Rho GTPase family member, Rac1, promotes chondrogenesis. Pharmacological inhibition of Rac1 expression in micromass culture resulted in reduced mRNA levels of the chondrogenic markers collagen II and aggrecan, and decreased accumulation of glycosaminoglycans. Expression of the essential chondrogenic transcription factors Sox9, Sox5, and Sox6 was also reduced upon inhibition of Rac1 signaling. In contrast, overexpression of Rac1 in the chondrogenic ATDC5 cell line increased mRNA transcripts of Sox9, 5, and 6, collagen II, and aggrecan. Inhibition of Rac1 resulted in a reduction in the number, size, and organization of cellular condensations and decreased expression of N-cadherin. Overexpression of Rac1 resulted in an increase in N-cadherin expression levels. Furthermore, genetic ablation of Rac1 in primary micromass cultures resulted in reduced expression of chondrogenic markers. Additionally, we provide evidence that Cdc42 also promotes chondrogenesis. Overexpression of Cdc42 in ATDC5 cells resulted in increased expression of Sox5, Sox9, and collagen II but not Sox6, aggrecan, or N-cadherin. Therefore, we demonstrate that Rac1 and Cdc42 are positive regulators of chondrogenesis, but act at least in part through different cellular and molecular mechanisms.
- Subjects :
- Animals
Chondrogenesis
DNA-Binding Proteins metabolism
Gene Expression Regulation
High Mobility Group Proteins metabolism
Lectins metabolism
Limb Buds metabolism
Mice
Models, Biological
Neuropeptides metabolism
RNA, Messenger metabolism
SOXB1 Transcription Factors
Signal Transduction
cdc42 GTP-Binding Protein metabolism
rac GTP-Binding Proteins metabolism
rac1 GTP-Binding Protein
Cadherins metabolism
Chondrocytes metabolism
Mesoderm metabolism
Neuropeptides physiology
rac GTP-Binding Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17573353
- Full Text :
- https://doi.org/10.1074/jbc.M700680200