Prolonged application of high fluid shear to chondrocytes recapitulates gene expression profiles associated with XXXX .

@entity1 @entity32 @entity1844 @entity8172 @entity571 @entity26 @entity3840
BACKGROUND: Excessive mechanical loading of articular cartilage producing hydrostatic stress, tensile strain and fluid flow leads to irreversible @entity1844 . Since application of high fluid shear to chondrocytes recapitulates some of the earmarks of OA, we aimed to screen the gene expression profiles of shear-activated chondrocytes and assess potential similarities with OA chondrocytes. METHODOLOGY/PRINCIPAL FINDINGS: Using a cDNA microarray technology, we screened the differentially-regulated genes in @entity1 T/C-28a2 chondrocytes subjected to high fluid shear (20 dyn/cm(2)) for 48 h and 72 h relative to static controls. Confirmation of the expression patterns of select genes was obtained by qRT-PCR. Using significance analysis of microarrays with a 5% false discovery rate, 71 and 60 non-redundant transcripts were identified to be >= 2-fold up-regulated and  <=0.6-fold down-regulated, respectively, in sheared chondrocytes. Published data sets indicate that 42 of these genes, which are related to extracellular matrix/degradation, cell proliferation/differentiation, @entity32 and cell survival/death, are differentially-regulated in OA chondrocytes. In view of the pivotal role of @entity3840 ( @entity3840 ) in the pathogenesis and/or progression of OA in vivo and regulation of shear-induced @entity32 and apoptosis in vitro, we identified a collection of genes that are either up- or down-regulated by shear-induced @entity3840 . @entity3840 and @entity8172 ( @entity8172 ) induce reactive @entity26 species production, and negatively regulate genes of the histone and cell cycle families, which may play a critical role in chondrocyte death. CONCLUSIONS/SIGNIFICANCE: Prolonged application of high fluid shear stress to chondrocytes recapitulates gene expression profiles associated with @entity571 . Our data suggest a potential link between exposure of chondrocytes/cartilage to abnormal mechanical loading and the pathogenesis/progression of OA.
