Evaluation of differentially expressed genes by shear stress in human osteoarthritic chondrocytes in vitro.

BACKGROUND The pathogenesis of osteoarthritis is related to abnormal mechanical stresses that alter cartilage metabolism and chondrocyte survival. Among the mechanical stresses, shear stress is held responsible for the development of arthritis. METHODS Monolayer cultures of human osteoarthritic chondrocytes were subjected to fluid-induced shear stress in vitro. A cDNA microarray technology was used to screen the differentially regulated genes and quantitative real-time poly-merase chain reaction (Q-RT-PCR) was used to confirm the results. The significance of the expression ratio for each gene was determined on the lowest associated false discovery rate calculated from the changes of gene expression in relation to the standard deviation of repeated measurements for that gene. RESULTS Exposure of human osteoarthritic chondrocytes to shear stress (0.82 Pa) for 2 hours differentially regulated 373 and 227 clones in two independent microarray analyses with at least a 1.7-fold change. By comparing the differentially regulated clones, 14 upregulated and 6 downregulated genes were identified. Many of the differentially expressed genes were related to cell proliferation/differentiation (TGF-beta, acidic FGF), cell survival/apoptosis (CYP1B1, BCL2L3, TNFRSF11B, chemokine ligands, ADM), and matrix homeostasis (DCN, SDC2, MGP, WISP2). CONCLUSION The gene expression patterns following shear stress show a high similarity to the gene expression in the reparative process of osteoarthritis chondrocytes. Using microarray analysis, this study suggests a close interaction between shear stress and the pathogenesis of osteoarthritis.