Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants

Chondrocytes are known to sense and respond to mechanical and physicochemic al stimuli by multiple regulatory pathways, including upstream signaling, t ranscription, translation, posttranslational modifications, and vesicular t ransport. Due to the complexity of identifying the biophysical phenomena th at occur during cartilage loading in vivo, the regulatory mechanisms that g overn chondrocyte mechanotransduction are not fully understood. Recent stud ies have shown that fluid flow during dynamic compression of cartilage expl ants can stimulate proteoglycan and protein synthesis. In this study, we ex amined the effect of deformations of cell and extracellular matrix on chond rocyte biosynthesis. We used tissue shear loading, since tissue shear cause s little volumetric deformation and can thereby decouple fluid flow from ce ll and matrix deformation. Shear loading was applied over a wide range of f requencies, 0.01-1.0 Hz, using 1-3% sinusoidal shear strain amplitudes, and the resulting proteoglycan and protein syntheses were measured using radio label incorporation. In addition, quantitative autoradiography was used to investigate spatial variations in matrix biosynthesis and to correlate thes e variations with the spatial profiles of biophysical stimuli. Our data sho w that tissue shear loading at 1-3% strain amplitude stimulated the synthes is of protein by similar to 50% and proteoglycans by similar to 25% at freq uencies between 0.01 and 1.0 Hz. The relatively uniform patterns of biosynt hesis in the radial and vertical directions within cylindrical explants rev ealed by autoradiography suggest that the stimulatory effect was associated with the relatively uniform deformation caused by simple shear loading. Th ese results suggest that chondrocytes can respond to tissue shear stress-in itiated pathways for the production of collagen and proteoglycan, which inc lude deformation of cells and pericellular matrix, even in the absence of m acroscopic tissue-level fluid flow. (C) 2001 Academic Press.