HYALURONAN METABOLISM IN RESPONSE TO MECHANICAL STRAIN IS MODULATED BY MATRIX DEPLETION

ABSTRACT Many studies have highlighted the importance of movement-induced mechanical stimuli in the development of functional synovial joints. However, such phenomenological results have failed to provide a full explanation of the mechanism essential for the morphogenesis of fluid-filled joint cavities. We have previously demonstrated that the large glycosaminoglycan hyaluronan (HA) in association with its principal cell surface receptor CD44, play a major role during the morphogenesis of chick joints (see Osbourne et al., in this volume). Here, we have taken cells from the surface of recently cavitated joints and subjected them to a brief period of dynamic mechanical strain (3800 μE for 10 minutes) and measured changes in HA synthesis/release and HA synthase gene expression. In addition, we have subjected cells to matrix-depletion prior to the application of mechanical strain in order to examine any potential modulatory function of the extracellular matrix during the cell's response to strain. Removal of the cell-associated HA-containing matrix with hyaluronidase significantly increases the release of HA into tissue culture media over 24 hours and is associated with alterations in HA synthase gene expression. Such changes in HA release are shown to be synergistically enhanced by the application of dynamic mechanical strain. These results show that cell-matrix interactions modify the response of embryonic cells to mechanical strain and provide further insight into mechano-dependent mechanisms of joint cavity morphogenesis.