Insulin-like growth factor-I diminishes the activation status and expression of the small GTPase Cdc42 in articular chondrocytes.

TitleInsulin-like growth factor-I diminishes the activation status and expression of the small GTPase Cdc42 in articular chondrocytes.
Publication TypeJournal Article
Year of Publication2004
AuthorsFortier LA, Deak MM, Semevolos SA, Cerione RA
JournalJournal of orthopaedic research : official publication of the Orthopaedic Research Society
Volume22
Issue2
Pagination436-45
Date Published2004 Mar
ISSN0736-0266
KeywordsAnimals, Cartilage, Articular, cdc42 GTP-Binding Protein, Cells, Cultured, Chondrocytes, Collagen Type II, Cytoskeleton, GTPase-Activating Proteins, Guanine Nucleotide Exchange Factors, Horses, Insulin-Like Growth Factor I, Matrix Metalloproteinase 3, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction
Abstract

Insulin-like growth factor-I (IGF-I) is an important anabolic growth factor in the maintenance of articular cartilage phenotypic expression. Chondrocyte morphology is also tightly linked to phenotype. The small G-protein Cdc42 plays a key role in regulation of cell morphology and phenotypic expression in several cell types and, we show here, in articular chondrocytes. The purpose of these studies was to investigate possible links between the intracellular signaling pathways of IGF-I and Cdc42 in articular chondrocytes. Treatment of chondrocytes with IGF-I resulted in a rapid and sustained decrease in the activation state (decreased GTP-bound) of Cdc42. Nucleotide exchange and hydrolysis experiments suggest that the decreased activation occurs through increased hydrolysis. Transient expression of dominant-negative Cdc42(T17N) allowed for enhanced expression of normal chondrocyte phenotype as determined by increased mRNA expression of collagen type II (Coll II) with decreased matrix metalloproteinase-3 (MMP-3) expression. The results of these studies suggest a novel link between IGF-I and Cdc42 signaling pathways. Further, an additional mechanism for the regulation of chondrocyte phenotype is defined through the IGF-I induced down-regulation of Cdc42 activation.

DOI10.1016/j.orthres.2003.08.021
Alternate JournalJ. Orthop. Res.