Chondrocytes maintain cartilage by transducing joint load into appropriate biosynthetic activity, a process commonly known as mechanotransduction. Malfunctioning mechanotransduction leads to cartilage degradation and osteoarthritis. The mechanism of mechanotransduction is only partially understood but osmotic stresses are thought to play an important role. This study shows that the chondrocyte nucleus shrinks and wrinkles under hyper-osmotic stress. It shrinks because the chromatin inside the nucleus contracts as the macromolecules in the cell become more crowded. It wrinkles because the nuclear lamina buckles as the nucleus contracts. These morphological changes accelerate transport across the nuclear envelope. Many cells have organized actin caps around their nuclei that constrain the nucleus from contracting under hyper-osmotic stress. Agents exist that can reverse this loss of osmotic sensitivity in vitro without damaging the cell.