Mechanical forces influence articular cartilage structure by regulating the activity of the cells - chondrocytes. Optimal mechanical stimulation maintains cartilage in a healthy state but abnormal forces lead to cartilage breakdown and the development of osteoarthritis. We have shown previously that mechanical stimulation of chondrocytes activates intracellular signalling cascades that regulate production of molecules important in maintaining cartilage structure (1, 2). These responses are altered in chondrocytes from osteoarthritic cartilage (3). Much of the research to date has investigated the effect of compressive forces on cartilage. However, within the joint, both compressive and shearing forces are important in the maintenance of cartilage and stimulation of chondrocyte function. We have been utilising a shear cell developed within the Department of Physics that enables us to stimulate cells within a 3D matrix with varying amounts of shear. Combining the use of this novel piece of equipment with fluorescent dyes that are commercially available for the imaging of live cells, we have been able to measure the responses of cells isolated from both normal and diseased tissue. Using the multiphoton and confocal microscope, we have obtained preliminary data on the responses of normal and diseased cells, and on responses of the same cell-type to different stimuli. We now aim to investigate these further. Understanding how the different forces affect normal and diseased cells will be critical to be able to understand the process that leads to cartilage degradation and the disease of osteoarthritis.

References

1. "Integrin-regulated secretion of interleukin-4: a novel pathway of mechanotransduction in human articular chondrocytes", S J Millward-Sadler, M O Wright, K Nishida, H Caldwell, G Nuki, and D M Salter, J. Cell Biol., 145, p183-189.
2. "Cyclical mechanotransduction regulates aggrecan and matrix metalloproteinase 3 mRNA levels in normal but not osteoarthritic human articular chondrocytes", S J Millward-Sadler, M O Wright, L W Davies, G Nuki, and D M Salter, Arthritis Rheum., 43, p2091-2099.
3. "Chondrocytes derived from osteoarthritic cartilage show an altered electrophysiological response to mechanical stimulation", S J Millward-Sadler, M O Wright, H-S Lee, H Caldwell, G Nuki and D M Salter, OA Cart., 8, p272-278.