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STUDY DESIGN An in vitro study to investigate the effect of pressure stimulation on nucleus pulposus (NP) cells. OBJECTIVE The aim of this study was to investigate the question whether physical stimulation can be leveraged to enhance extracellular matrix (ECM) synthesis as a preventive measure for intervertebral disc (IVD) degeneration. SUMMARY OF BACKGROUND DATA ECM plays an important role in regulating hydration and pressure balance of the IVD. METHODS Cellular stimulation devices with different pressurizing protocols were used to create a pressurized environment to cells cultures. The setup was used to mimic the pressurized conditions within IVD to investigate the effect of pressure stimulation on NP cells. RESULTS Pressure stimulation at 300 kPa can enhance the synthesis of ECM proteins Collagen II and aggrecan in NP cells and the effect of dynamic pressure stimulation outperformed the static one. The difference between static and dynamic pressure stimulation was due primarily to calcium signaling activated by pressure fluctuation. The superior effect of dynamic pressure holds for a wide range of stimulation durations, relating to the range of spontaneous calcium oscillations in NP cells. CONCLUSION The results link mechanotransduction to the downstream ECM protein synthesis and suggest slow exercises that correspond with spontaneous calcium oscillations in NP cells can be effective to stimulate ECM synthesis in IVD.Level of Evidence: 4.