RhoA/ROCK signaling regulates chondrogenesis in a context-dependent manner.

作者: Anita Woods , Frank Beier

DOI: 10.1074/JBC.M509433200

关键词: Cytochalasin DRHOABiologyCytochalasinCartilage metabolismCell biologySignal transductionAggrecanRegulation of gene expressionChondrogenesisMolecular biology

摘要: The development of the cartilage template that precedes endochondral bone formation requires condensation mesenchymal cells and their subsequent differentiation to chondrocytic lineage. We have previously shown inhibition RhoA/ROCK signaling pathway or actin dynamics enhances Sox9 mRNA expression, increases glycosaminoglycan production, transforms cell shape a spherical, chondrocyte-like morphology. However, we demonstrate here in three-dimensional micromass cultures cells, increased expression response these manipulations is not sufficient induce established target genes. This illustrated by decrease transcript levels collagen II aggrecan as well reduced activity Sox9-responsive reporter gene ROCK cytochalasin D. also transcriptional co-activators L-Sox5 Sox6 upon likely partially due but delay phosphorylation following inhibition. In contrast, D treatment monolayer culture results enhancement number markers chondrogenesis such transcripts levels. These data effects polymerization inhibitors on chondrogenic are dependent cellular context.

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