PMID- 15013107
OWN - NLM
STAT- MEDLINE
DCOM- 20040324
LR  - 20071114
IS  - 0736-0266 (Print)
IS  - 0736-0266 (Linking)
VI  - 22
IP  - 2
DP  - 2004 Mar
TI  - Insulin-like growth factor-I diminishes the activation status and expression of 
      the small GTPase Cdc42 in articular chondrocytes.
PG  - 436-45
AB  - 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.
FAU - Fortier, Lisa A
AU  - Fortier LA
AD  - Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA. 
      laf4@cornell.edu
FAU - Deak, Molly M
AU  - Deak MM
FAU - Semevolos, Stacy A
AU  - Semevolos SA
FAU - Cerione, Richard A
AU  - Cerione RA
LA  - eng
GR  - AG00905/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Collagen Type II)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (RNA, Messenger)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Chondrocytes/*drug effects/metabolism
MH  - Collagen Type II/genetics/metabolism
MH  - Cytoskeleton/drug effects
MH  - GTPase-Activating Proteins/metabolism
MH  - Guanine Nucleotide Exchange Factors/metabolism
MH  - Horses
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - cdc42 GTP-Binding Protein/*biosynthesis
EDAT- 2004/03/12 05:00
MHDA- 2004/03/25 05:00
CRDT- 2004/03/12 05:00
PHST- 2003/05/09 00:00 [received]
PHST- 2003/08/12 00:00 [accepted]
PHST- 2004/03/12 05:00 [pubmed]
PHST- 2004/03/25 05:00 [medline]
PHST- 2004/03/12 05:00 [entrez]
AID - S0736026603002110 [pii]
AID - 10.1016/j.orthres.2003.08.021 [doi]
PST - ppublish
SO  - J Orthop Res. 2004 Mar;22(2):436-45. doi: 10.1016/j.orthres.2003.08.021.