title: Interleukin-1α, -6, and -8 decrease Cdc42 activity resulting in loss of articular chondrocyte phenotype.
abstract: Small GTPase proteins mediate changes in cellular morphology and other cellular functions. The aim of this study was to examine signaling of the small GTPase Cdc42 by stimulating chondrocytes grown in monolayer with long- (96 h) or short- (2 and 30 min) term exposure to interleukin-1α (IL-1α), IL-6, or IL-8. Quantitative PCR was used to determine changes in collagen type IIB (COL2A1), aggrecan (AGG), and matrix metalloproteinase-13 (MMP-13) gene expression after prolonged cytokine exposure. Effects of short-term treatment with IL-α, IL-6, or IL-8 on endogenous GTP-bound Cdc42 levels were assessed using an affinity assay, and on actin filament organization using confocal microscopy. Cytokine treatments significantly decreased COL2A1 and AGG expression and increased MMP-13 expression. Short exposure to IL-1α, IL-6, or IL-8 decreased endogenous GTP-Cdc42 and increased stress fibers, which were reversed with cytochalasin D treatment. These results show that IL-mediated Cdc42 signaling modifies chondrocyte phenotype and morphology. This may lend insight into the altered chondrocyte phenotype in catabolic conditions such as osteoarthritis.
authors.affiliation: Department of Clinical Sciences, VMC, Cornell University, C3-181, Ithaca, New York 14853, USA.
authors.forename: Kira D
authors.initials: KD
authors.lastname: Novakofski
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Torre
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Fortier
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000032:analysis; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis; D006736:Horses; D053582:Interleukin-1alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D010641:Phenotype; D022502:Stress Fibers / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000032:analysis* / Q000502:physiology
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016209:Interleukin-8; D020764:cdc42 GTP-Binding Protein