|
| Healthy IVD | IDD |
|
| Avascularity | Vessels from the vertebral bodies branch into capillaries terminating in the CEP [21] | CEP calcification may hinder nutrient diffusion [39] |
| Hypoxia | Oxygen concentration decreases from AF surfaces (19.5%) to the inner portion of the NP (0.65%) [40] | Oxygen concentration falls due to reduced blood supply and shift of NP cell metabolism towards oxidative phosphorylation [41] |
| Low glucose concentration | Glucose concentration is higher at IVD boundaries while it falls towards the center of the NP [42] | Glucose levels diminish together with blood supply and increased consumption by degenerative cells [43] |
| Acidity | Due to anaerobic glycolysis and lactic acid production, average pH is 7.0-7.2 [38] | pH may decrease to 6.5 in mild IDD and 5.6 in severe IDD due to nutrient depletion and increase lactic acid production [38] |
| Hyperosmolarity | The high GAG content within the NP determines a high osmolarity which varies upon mechanical load (430-500 mOsm/L) [44] | The loss of proteoglycans due to matrix breakdown reduces IVD osmolarity [45] |
| Mechanical loading | Mechanical stimuli (flexion, torsion, shear, and compression) regulate IVD cell activity and metabolism within a physiological range (0.1-2.5 MPa) [46, 47] | Disruption of IVD structure alters loading transmission across the IVD and the vertebral segments, resulting in tissue damage and cellular overstress [48] |
| Inflammation | Proinflammatory cytokines and chemokines may have a role in IVD development and recruitment of local progenitor cells [49, 50] | The excess of proinflammatory cytokines increases cell apoptosis, senescence, autophagy, matrix breakdown, and discogenic LBP [51] |
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