Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow

Chondrogenesis in cartilage development and repair and cartilage degenerati on in arthritis can be regulated by mechanical-laod-induced physical factor s such as tissue deformation, interstitial fluid flow and pressure, and ele ctrical fields or streaming potentials. Previous animal and tissue explant studies have shown that time-varying dynamic tissue loading can increase th e synthesis and deposition of matrix molecules in an amplitude-, frequency- , and spatially dependent manner, To provide information on the cell-level physical factors which may stimulate chondrocytes to increase production an d export of aggrecan, the main proteoglycan component of the cartilage matr ix, we characterized local changes in aggrecan synthesis within cyclically loaded tissue explant disks and compared those changes to values of predict ed local physical factors, Aggrecan synthesis following a 23-h compression/ radiolabel protocol was measured with a spatial resolution of similar to 0. 1 mm across the 1.5-mm radius of explanted disks using a quantitative autor adiography method, A uniform stimulation of aggrecan synthesis was observed at an intermediate frequency of 0.01 Hz, while, at a higher frequency of 0 .1 Hz, stimulation was only seen at peripheral radial positions. Profiles o f radial solid matrix deformation and interstitial fluid pressure and veloc ity predicted to be occurring across the radius of the disk during sinusoid al loading were estimated using a composite poroelastic model, Tissue regio ns experiencing high interstitial fluid velocities corresponded to those di splaying increased aggrecan synthesis. These results reinforce the role of load-induced how of interstitial fluid in the stimulation of aggrecan produ ction during dynamic loading of cartilage. (C) 1999 Academic Press.