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OBJECTIVE: The nucleus pulposus (NP) of the intervertebral disc develops from the notochord. Humans and other species in which notochordal cells (NCs) disappear to be replaced by chondrocyte-like mature NP cells (MNPCs) frequently develop disc degeneration, unlike other species that retain NCs. The reasons for NC disappearance are unknown. In humans, the change in cell phenotype (to MNPCs) coincides with changes that decrease nutrient supply to the avascular disc. We undertook this study to test the hypothesis that the consequent nutrient stress could be associated with NC disappearance. METHODS: We measured cell densities and metabolic rates in 3-dimensional cultures of porcine NCs and bovine MNPCs, and we determined survival rates under conditions of nutrient deprivation. We used scanning electron microscopy to examine end plate porosity of discs with NCs and those with MNPCs. Nutrient-metabolite profiles and cell viability were calculated as a function of cell density and disc size in a consumption/diffusion mathematical model. RESULTS: NCs were more active metabolically and more susceptible to nutrient deprivation than were MNPCs. Hypoxia increased rates of glycolysis in NCs but not in MNPCs. Higher end plate porosity in discs with NCs suggested greater nutrient supply in keeping with higher nutritional demands. Mathematical simulations and experiments using an analog disc diffusion chamber indicated that a fall in nutrient concentrations resulting from increased diffusion distance during growth and/or a fall in blood supply through end plate changes could instigate NC disappearance. CONCLUSION: NCs demand more energy and are less resistant to nutritional stress than MNPCs, which may shed light on the fate of NCs in humans. This provides important information about prospective NC tissue engineering approaches.

Original publication




Journal article


Arthritis Rheum

Publication Date





1026 - 1034


Animals, Blood Proteins, Carbon Dioxide, Cattle, Cell Count, Cells, Cultured, Chondrocytes, Diffusion, Energy Metabolism, Glucose, Glycolysis, Growth Plate, Hydrogen-Ion Concentration, Imaging, Three-Dimensional, Intervertebral Disc, Lactic Acid, Microscopy, Electron, Scanning, Notochord, Oxidative Phosphorylation, Oxygen, Oxygen Consumption, Swine, Tissue Engineering