Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose

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Abstract
Articular cartilage is subjected to dynamic compressive loading that is known to influence chondrocyte metabolism. While the exact signalling mechanisms are unclear, it has been proposed that cell deformation plays a role and may stimulate a metabolic response through distinctive pathways. In this study, a well characterized model system in which chondrocytes are embedded in agarose was used to study the effect of dynamic cellular strain on three key metabolic processes, namely the synthesis of glycosaminoglycan, of DNA, and of total protein. Using a specially designed apparatus, 15% compressive strain amplitude was applied to agarose-chondrocyte cylinders statically or dynamically over a range of frequencies (0.3-3 Hz). Static and low-frequency strain (0.3 Hz) inhibited the synthesis of glycosaminoglycan, while a frequency of 1 Hz stimulated synthesis. Static strain reduced the level of thymidine uptake, whereas dynamic strain at all frequencies induced an increase in chondrocyte proliferation. Incorporation of tritiated proline was suppressed by all strain regimens tested. The three parameters investigated were each influenced by the dynamic strain regimens in a distinct manner, implying that the signalling mechanisms involved are uncoupled.