Cartilage compression results in changes in the shape, volume as well as hydrostatic and osmotic pressure of chondrocytes in situ. For example, changes in the cellular osmotic environment have been shown to modulate chondrocyte biosynthesis and gene expression, however, the mechanosensing mechanisms mediating these responses are relatively unknown. Nuclear shape and size changes resulting from cell deformation have been suggested to alter cell functions, and as such we recently performed a study that reported that chondrocytes and their nuclei respond to osmotic loading with alterations in their size. In the current study, we focus on the potential role of the actin cytoskeleton in mediating the transmission of osmotic loading-induced cell size changes to the nucleus.