MECHANICAL COMPRESSION MODULATES MATRIX BIOSYNTHESIS IN CHONDROCYTE AGAROSE CULTURE

This study focuses on the effect of static and dynamic mechanical comp ression on the biosynthetic activity of chondrocytes cultured within a garose gel, Chondrocyte/agarose disks (3 mm diameter) were placed betw een impermeable platens and subjected to uniaxial unconfined compressi on at various times in culture (2-43 days), [S-35]sulfate and [H-3]pro line radiolabel incorporation were used as measures of proteoglycan an d protein synthesis, respectively, Graded levels of static compression (up to 50%) produced little or no change in biosynthesis at very earl y times, but resulted in significant decreases in synthesis with incre asing compression amplitude at later times in culture; the latter obse rvation was qualitatively similar to that seen in intact cartilage exp lants, Dynamic compression of similar to 3% dynamic strain amplitude ( similar or equal to 30 mu m displacement amplitude) at 0.01-1.0 Hz, su perimposed on a static offset compression, stimulated radiolabel incor poration by an amount that increased with time in culture prior to loa ding as more matrix was deposited around and near the cells, This stim ulation was also similar to that observed in cartilage explants, The p resence of greater matrix content at later times in culture also creat ed differences in biosynthetic response at the center versus near the periphery of the 3 mm chondrocyte/agarose disks, The fact that chondro cyte response to static compression was significantly affected by the presence or absence of matrix, as were the physical properties of the disks, suggested that cell-matrix interactions (e.g. mechanical and/or receptor mediated) and extracellular physicochemical effects (increas ed [Na+], reduced pH) may be more important than matrix-independent ce ll deformation and transport limitations in determining the biosynthet ic response to static compression, For dynamic compression, fluid flow , streaming potentials, and cell-matrix interactions appeared to be mo re significant as stimuli than the small increase in fluid pressure, a ltered molecular transport, and matrix-independent cell deformation, T he qualitative similarity in the biosynthetic response to mechanical c ompression of chondrocytes cultured in agarose gel and chondrocytes in intact cartilage further indicates that gel culture preserves certain physiological features of chondrocyte behavior and can be used to inv estigate chondrocyte response to physical and chemical stimuli in a co ntrolled manner.