Activation of SMAD2 upon compressive load occurs exclusively in regions of cartilage where matrix stiffness is relatively low

Mechanical force is an important factor affecting the health of articular cartilage and consequently the function of the joint. Work from our lab has identified an important mechanotransducing role for the pericellular matrix (PCM) of cartilage; sequesteringregulatory molecules such as fibroblastic growth factor 2 (FGF2), latent transforming growth factor beta (TGFβ) and connective tissue growth factor (CTGF). In unloaded cartilage these molecules are held back from the cell surface, but upon mechanical stimulation they are released allowing them to diffuse to the cell surface and activate the cell (Vincent et al. 2007, and unpublished results). Data presented at OARSI 2014 and 2015 revealed that CTGF and latent TGFβ are released together and phosphorylate SMAD2 upon cartilage injury. In this study, we aimed to build on these observations by determining if cellular responses to compressive load vary with depth from the articular surface and with the local mechanical stiffness of the matrix