Development of a Porcine Model to Assess the Effect of In Situ Knee Joint Loading on Site-Specific Cartilage Gene Expression

Abstract

Abstract Cyclic mechanical loading of cartilage induces stresses and fluid flow, which are thought to modulate chondrocyte metabolism. The uneven surface, plus the heterogeneity of cartilage within a joint, makes stress and fluid pressure distribution in the tissue nonuniform, and gene expression may vary at different sites as a function of load magnitude, frequency, and time. In previous studies, cartilage explants were used for loading tests to investigate biological responses of the cartilage to mechanical loading. In contrast, we used loading tests on intact knee joints, to better reflect the loading conditions in a joint, and thus provide a more physiologically relevant mechanical environment. Gene expression levels in loaded samples for a selection of relevant genes were compared with those of the corresponding unloaded control samples to characterize potential differences. Furthermore, the effects of load magnitude and duration on gene expression levels were investigated. We observed differences in gene expression levels between samples from different sites in the same joint and between corresponding samples from the same site in loaded and unloaded joints. Consistent with previous findings, our results indicate that there is a critical upper and lower threshold of loading for triggering the expression of certain genes. Variations in gene expression levels may reflect the effect of local loading, topography, and structure of the cartilage in an intact joint on the metabolic activity of the associated cells.