The involvement of XXXX and @entity3646 in the response of @entity1 annulus fibrosus cells to cyclic tensile strain: an altered mechanotransduction pathway with degeneration.

@entity1 @entity1797 @entity1193 @entity1549 @entity1192 @entity27369 @entity3646
INTRODUCTION: Recent evidence suggests that intervertebral disc (IVD) cells derived from degenerative tissue are unable to respond to physiologically relevant mechanical stimuli in the 'normal' anabolic manner, but instead respond by increasing matrix catabolism. Understanding the nature of the biological processes which allow disc cells to sense and respond to mechanical stimuli (a process termed 'mechanotransduction') is important to ascertain whether these signalling pathways differ with disease. The aim here was to investigate the involvement of @entity1192 and @entity3646 in the response of annulus fibrosus (AF) cells derived from nondegenerative and degenerative tissue to cyclic tensile strain to determine whether cytokine involvement differed with @entity1797 . METHODS: AF cells were isolated from nondegenerative and degenerative @entity1 IVDs, expanded in monolayers and cyclically strained in the presence or absence of the cytokine inhibitors @entity1192 receptor antagonist ( @entity1193 ) or @entity3646 receptor antibody (IL-4RAb) with 10% strain at 1.0 Hz for 20 minutes using a Flexcell strain device. Total RNA was extracted from the cells at time points of baseline control and 1 or 24 hours poststimulation. Quantitative real-time polymerase chain reaction was used to analyse the gene expression of matrix proteins (aggrecan and type I collagen) and enzymes ( @entity1549 ( @entity1549 ) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 4 ( @entity27369 )). RESULTS: Expression of catabolic genes ( @entity1549 and @entity27369 ) decreased in AF cells derived from nondegenerative tissue in response to 1.0-Hz stimulation, and this decrease in gene expression was inhibited or increased following pretreatment of cells with @entity1193 or IL-4RAb respectively. Treatment of AF cells derived from degenerative tissue with an identical stimulus (1.0-Hz) resulted in reduced anabolic gene expression (aggrecan and type I collagen), with @entity1193 or IL-4RAb pretreatment having no effect. CONCLUSIONS: Both @entity1192 and @entity3646 are involved in the response of AF cells derived from nondegenerative tissue to 1.0-Hz cyclic tensile strain. Interestingly, the altered response observed at 1.0-Hz in AF cells from degenerative tissue appears to be independent of either cytokine, suggesting an alternative mechanotransduction pathway in operation.
