RRC ID 6560
Author Itoh S, Kanno S, Gai Z, Suemoto H, Kawakatsu M, Tanishima H, Morimoto Y, Nishioka K, Hatamura I, Yoshida M, Muragaki Y.
Title Trps1 plays a pivotal role downstream of Gdf5 signaling in promoting chondrogenesis and apoptosis of ATDC5 cells.
Journal Genes Cells
Abstract Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant skeletal disorder caused by mutations of TRPS1. Based on the similar expression patterns of Trps1 and Gdf5, we hypothesized a possible functional interaction between these two molecules. Using a chondrogenic cell line (ATDC5), we investigated the association of Gdf5-mediated signaling pathways with Trps1 and the phenotypic changes of ATDC5 cells due to over-expression or suppression of Trps1. Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1. Trps1-overexpressing ATDC5 (O/E) cells differentiated into chondrocytes more quickly than mock-infected control cells, whereas cells transfected with dn-Alk6 showed slower differentiation. On the other hand, O/E cells showed an increase of apoptosis along with the up-regulation of cleaved caspase 3 and down-regulation of Bcl-2, whereas dn-Alk6 cells showed suppression of apoptosis. In conclusion, Trps1 acts downstream of the Gdf5 signaling pathway and promotes the differentiation and apoptosis of ATDC5 cells.
Volume 13(4)
Pages 355-63
Published 2008-4-1
DOI 10.1111/j.1365-2443.2008.01170.x
PMID 18363966
MeSH Animals Apoptosis / physiology* Base Sequence Bone Diseases, Developmental / genetics Bone Morphogenetic Protein Receptors, Type I / genetics Bone Morphogenetic Protein Receptors, Type I / metabolism Bone Morphogenetic Proteins / metabolism* Cell Line Chondrogenesis / physiology* Craniofacial Abnormalities / genetics DNA Primers / genetics Feedback GATA Transcription Factors / genetics GATA Transcription Factors / metabolism* Gene Expression Growth Differentiation Factor 5 Mice Phenotype Repressor Proteins Signal Transduction Transfection p38 Mitogen-Activated Protein Kinases / metabolism
IF 1.655
Times Cited 25
Human and Animal Cells ATDC5(RCB0565)