Mechanical Regulation of Cartilage Biosynthetic Behavior: Physical Stimuli

Abstract

The biosynthetic response of calf cartilage disk explants to small-amplitude dynamic compression was studied in radially unconfined compression over a wide range of frequencies. The relative importance of oscillatory fluid flow, hydrostatic pressure, streaming potential, and cell deformation in modulating chondrocyte metabolism was explored by quantifying the frequency dependence and the spatial (radial) distribution of the biosynthetic response within the 3-mm-diameter explant disks. At frequencies greater than 0.001 Hz (cycle/s), dynamic compression increased biosynthesis of proteoglycans and proteins. While compression at frequencies between 0.002 and 0.01 Hz caused a stimulation of biosynthesis that was distributed throughout the disk, compression at 0.1 Hz caused a stimulation that was confined mainly to the outer radial periphery. These distributions were compared to previous estimates of the radial distribution of physical forces and flows within the matrix. The results suggest that the stimulation of chondrocyte biosynthesis by dynamic mechanical compression at amplitudes up to 10% (stresses up to 0.5 MPa) is related to changes in fluid flow and/or cell shape rather than changes in hydrostatic pressure. Since static compression to the original cut thickness caused a slight decrease in biosynthesis in the center of the disks, we also studied the possible role of limited diffusive transport in the marked inhibition of synthesis seen during large displacement static compression. Experiments in which the surface area-to-volume ratio of disks or the concentration of labeling substrate or serum were varied provided no evidence that limited diffusive transport was responsible for the inhibition of biosynthesis by large displacement static compression. Recovery of biosynthesis from static compression and histological analyses of compressed tissue suggested that there was no significant cell damage even during 12 h of 50% static compression.